Trial Outcomes & Findings for A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency (NCT NCT02476916)
NCT ID: NCT02476916
Last Updated: 2026-05-01
Results Overview
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
Up to Week 24
Results posted on
2026-05-01
Participant Flow
Participants took part in the study across multiple study sites in 6 countries from 26 June 2015 to 02 April 2025.
A total of 52 participants were enrolled in the Core Period of the study. Participants were randomized 1:1 to receive AG-348 50 mg or AG-348 300 mg. Participants who completed the 24-week Core Period, had clinical activity, and tolerated the AG-348 dose entered the Extension Period for up to 102 months.
Participant milestones
| Measure |
AG-348 50 mg BID
Participants with Pyruvate Kinase (PK) deficiency received AG-348, 50 mg, as initial dose, twice daily (BID) for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent Adverse Events (AEs) and Hemoglobin (Hb) levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
|
AG-348 300 mg BID
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.
|
|---|---|---|
|
Core Period (up to 24 Weeks)
STARTED
|
27
|
25
|
|
Core Period (up to 24 Weeks)
COMPLETED
|
21
|
22
|
|
Core Period (up to 24 Weeks)
NOT COMPLETED
|
6
|
3
|
|
Extension Period (Week 25- 102 Months)
STARTED
|
18
|
18
|
|
Extension Period (Week 25- 102 Months)
COMPLETED
|
1
|
2
|
|
Extension Period (Week 25- 102 Months)
NOT COMPLETED
|
17
|
16
|
Reasons for withdrawal
| Measure |
AG-348 50 mg BID
Participants with Pyruvate Kinase (PK) deficiency received AG-348, 50 mg, as initial dose, twice daily (BID) for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent Adverse Events (AEs) and Hemoglobin (Hb) levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
|
AG-348 300 mg BID
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.
|
|---|---|---|
|
Core Period (up to 24 Weeks)
Adverse Event
|
2
|
2
|
|
Core Period (up to 24 Weeks)
Physician Decision
|
1
|
1
|
|
Core Period (up to 24 Weeks)
Withdrawal by Participant
|
3
|
0
|
|
Extension Period (Week 25- 102 Months)
Adverse Event
|
1
|
0
|
|
Extension Period (Week 25- 102 Months)
Withdrawal by Participant
|
1
|
0
|
|
Extension Period (Week 25- 102 Months)
Physician Decision
|
5
|
5
|
|
Extension Period (Week 25- 102 Months)
Approved drug available for indication
|
5
|
6
|
|
Extension Period (Week 25- 102 Months)
Non-compliance with study drug
|
1
|
1
|
|
Extension Period (Week 25- 102 Months)
Lost to Follow-up
|
1
|
1
|
|
Extension Period (Week 25- 102 Months)
Reason not specified
|
3
|
3
|
Baseline Characteristics
A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency
Baseline characteristics by cohort
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
|
0 Participants
n=14 Participants
|
0 Participants
n=34 Participants
|
0 Participants
n=69 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
2 Participants
n=14 Participants
|
1 Participants
n=34 Participants
|
3 Participants
n=69 Participants
|
|
Age, Continuous
|
30.6 years
STANDARD_DEVIATION 11.20 • n=14 Participants
|
37.6 years
STANDARD_DEVIATION 12.02 • n=34 Participants
|
34.0 years
STANDARD_DEVIATION 12.01 • n=69 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=14 Participants
|
11 Participants
n=34 Participants
|
20 Participants
n=69 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=14 Participants
|
14 Participants
n=34 Participants
|
32 Participants
n=69 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=14 Participants
|
0 Participants
n=34 Participants
|
0 Participants
n=69 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=14 Participants
|
23 Participants
n=34 Participants
|
47 Participants
n=69 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=14 Participants
|
2 Participants
n=34 Participants
|
5 Participants
n=69 Participants
|
|
Race/Ethnicity, Customized
Race · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=14 Participants
|
0 Participants
n=34 Participants
|
0 Participants
n=69 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
0 Participants
n=14 Participants
|
0 Participants
n=34 Participants
|
0 Participants
n=69 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
22 Participants
n=14 Participants
|
21 Participants
n=34 Participants
|
43 Participants
n=69 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
1 Participants
n=14 Participants
|
2 Participants
n=34 Participants
|
3 Participants
n=69 Participants
|
|
Race/Ethnicity, Customized
Race · Unknown or Not Reported
|
2 Participants
n=14 Participants
|
1 Participants
n=34 Participants
|
3 Participants
n=69 Participants
|
PRIMARY outcome
Timeframe: Up to Week 24Population: The Safety Analysis Set included all participants who had received at least one dose of study drug.
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period
|
96.3 percentage of participants
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Month 102Population: The Safety Analysis Set included all participants who had received at least one dose of study drug.
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related. Safety data for cumulative period (Core period and Extension period) has been reported in this outcome measure.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Percentage of Participants Experiencing at Least One AE up to Month 102
|
100.0 percentage of participants
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Hemoglobin (Hb) Value at Week 24
Baseline
|
92.43 grams per liter (g/L)
Standard Deviation 14.760
|
86.36 grams per liter (g/L)
Standard Deviation 11.668
|
|
Change From Baseline in Hemoglobin (Hb) Value at Week 24
Change at Week 24
|
13.10 grams per liter (g/L)
Standard Deviation 13.644
|
16.65 grams per liter (g/L)
Standard Deviation 16.874
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=12 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=16 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline Hb Value up to Month 102
Change at Month 12
|
15.25 g/L
Standard Deviation 16.046
|
23.93 g/L
Standard Deviation 18.005
|
|
Change From Baseline Hb Value up to Month 102
Change at Month 36
|
23.14 g/L
Standard Deviation 8.212
|
25.23 g/L
Standard Deviation 13.009
|
|
Change From Baseline Hb Value up to Month 102
Change at Month 60
|
22.43 g/L
Standard Deviation 7.606
|
28.95 g/L
Standard Deviation 12.712
|
|
Change From Baseline Hb Value up to Month 102
Change at Month 84
|
20.14 g/L
Standard Deviation 8.037
|
26.92 g/L
Standard Deviation 17.440
|
|
Change From Baseline Hb Value up to Month 102
Change at Month 102
|
20.92 g/L
Standard Deviation 9.075
|
25.50 g/L
Standard Deviation 9.918
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Hematocrit at Week 24
Baseline
|
0.2881 fraction of 1
Standard Deviation 0.04494
|
0.2693 fraction of 1
Standard Deviation 0.03325
|
|
Change From Baseline in Hematocrit at Week 24
Change at Week 24
|
0.0360 fraction of 1
Standard Deviation 0.03916
|
0.0444 fraction of 1
Standard Deviation 0.04745
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=12 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=16 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Hematocrit up to Month 102
Change at Month 12
|
0.0428 fraction of 1
Standard Deviation 0.04823
|
0.0673 fraction of 1
Standard Deviation 0.04854
|
|
Change From Baseline in Hematocrit up to Month 102
Change at Month 36
|
0.0550 fraction of 1
Standard Deviation 0.02836
|
0.0598 fraction of 1
Standard Deviation 0.04136
|
|
Change From Baseline in Hematocrit up to Month 102
Change at Month 60
|
0.0565 fraction of 1
Standard Deviation 0.02264
|
0.0726 fraction of 1
Standard Deviation 0.03137
|
|
Change From Baseline in Hematocrit up to Month 102
Change at Month 84
|
0.0475 fraction of 1
Standard Deviation 0.02330
|
0.0690 fraction of 1
Standard Deviation 0.04855
|
|
Change From Baseline in Hematocrit up to Month 102
Change at Month 102
|
0.0482 fraction of 1
Standard Deviation 0.01296
|
0.0550 fraction of 1
Standard Deviation 0.04525
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Reticulocyte Count at Week 24
Baseline
|
459.39 cells * 10^9/liter
Standard Deviation 230.621
|
474.19 cells * 10^9/liter
Standard Deviation 233.868
|
|
Change From Baseline in Reticulocyte Count at Week 24
Change at Week 24
|
-73.77 cells * 10^9/liter
Standard Deviation 300.971
|
-3.96 cells * 10^9/liter
Standard Deviation 327.426
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline will be calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=11 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=15 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Reticulocyte Count up to Month 102
Change at Month 12
|
-272.65 cells * 10^9/liter
Standard Deviation 267.001
|
-32.51 cells * 10^9/liter
Standard Deviation 348.744
|
|
Change From Baseline in Reticulocyte Count up to Month 102
Change at Month 36
|
-225.83 cells * 10^9/liter
Standard Deviation 265.429
|
-83.61 cells * 10^9/liter
Standard Deviation 291.972
|
|
Change From Baseline in Reticulocyte Count up to Month 102
Change at Month 60
|
-188.36 cells * 10^9/liter
Standard Deviation 226.949
|
-106.67 cells * 10^9/liter
Standard Deviation 291.400
|
|
Change From Baseline in Reticulocyte Count up to Month 102
Change at Month 84
|
-157.58 cells * 10^9/liter
Standard Deviation 268.248
|
-161.47 cells * 10^9/liter
Standard Deviation 263.235
|
|
Change From Baseline in Reticulocyte Count up to Month 102
Change at Month 102
|
-64.06 cells * 10^9/liter
Standard Deviation 58.277
|
-293.01 cells * 10^9/liter
Standard Deviation 300.258
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=7 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Haptoglobin at Week 24
Baseline
|
0.360 g/L
Standard Deviation 0.2568
|
0.460 g/L
Standard Deviation 0.5362
|
|
Change From Baseline in Haptoglobin at Week 24
Change at Week 24
|
0.230 g/L
Standard Deviation 0.2475
|
0.260 g/L
Standard Deviation 0.4503
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Haptoglobin up to Month 102
Change at Month 12
|
0.343 g/L
Standard Deviation 0.3865
|
0.523 g/L
Standard Deviation 0.6261
|
|
Change From Baseline in Haptoglobin up to Month 102
Change at Month 36
|
0.135 g/L
Standard Deviation 0.2051
|
0.940 g/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
|
Change From Baseline in Haptoglobin up to Month 102
Change at Month 60
|
0.110 g/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
0.710 g/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
|
Change From Baseline in Haptoglobin up to Month 102
Change at Month 84
|
0.760 g/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
1.700 g/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
|
Change From Baseline in Haptoglobin up to Month 102
Change at Month 102
|
0.390 g/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
0.610 g/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all participants who were randomized. Overall number of participants analyzed is the number of participants with evaluable data. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=18 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=20 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Carboxyhemoglobin (COHb) at Week 24
Baseline
|
5.5 percentage Hb bound to CO
Standard Deviation 1.42
|
6.2 percentage Hb bound to CO
Standard Deviation 2.31
|
|
Change From Baseline in Carboxyhemoglobin (COHb) at Week 24
Change at Week 24
|
-1.3 percentage Hb bound to CO
Standard Deviation 2.26
|
-0.6 percentage Hb bound to CO
Standard Deviation 1.89
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 18, 24, and 30Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=7 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=10 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in COHb up to Month 30
Change at Month 12
|
0.0 percentage Hb bound to CO
Standard Deviation 1.73
|
-0.1 percentage Hb bound to CO
Standard Deviation 1.79
|
|
Change From Baseline in COHb up to Month 30
Change at Month 18
|
-0.7 percentage Hb bound to CO
Standard Deviation 1.63
|
-1.1 percentage Hb bound to CO
Standard Deviation 1.54
|
|
Change From Baseline in COHb up to Month 30
Change at Month 24
|
-1.0 percentage Hb bound to CO
Standard Deviation 2.00
|
-0.6 percentage Hb bound to CO
Standard Deviation 3.26
|
|
Change From Baseline in COHb up to Month 30
Change at Month 30
|
-0.2 percentage Hb bound to CO
Standard Deviation 0.84
|
-1.2 percentage Hb bound to CO
Standard Deviation 1.47
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24
Baseline
|
287.17 units per liter (U/L)
Standard Deviation 172.172
|
257.42 units per liter (U/L)
Standard Deviation 129.110
|
|
Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24
Change at Week 24
|
-36.74 units per liter (U/L)
Standard Deviation 140.291
|
-4.89 units per liter (U/L)
Standard Deviation 148.024
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 18, 24, and 30Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=12 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=17 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in LDH up to Month 30
Change at Month 12
|
-38.13 U/L
Standard Deviation 137.244
|
-33.78 U/L
Standard Deviation 155.946
|
|
Change From Baseline in LDH up to Month 30
Change at Month 18
|
-8.50 U/L
Standard Deviation 185.778
|
-29.92 U/L
Standard Deviation 166.593
|
|
Change From Baseline in LDH up to Month 30
Change at Month 24
|
-130.28 U/L
Standard Deviation 209.075
|
-76.30 U/L
Standard Deviation 169.040
|
|
Change From Baseline in LDH up to Month 30
Change at Month 30
|
-148.25 U/L
Standard Deviation 174.606
|
-73.84 U/L
Standard Deviation 169.661
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Total Bilirubin at Week 24
Baseline
|
92.91 micromole per liter (umol/L)
Standard Deviation 53.178
|
93.44 micromole per liter (umol/L)
Standard Deviation 54.169
|
|
Change From Baseline in Total Bilirubin at Week 24
Change at Week 24
|
-36.05 micromole per liter (umol/L)
Standard Deviation 34.231
|
-49.85 micromole per liter (umol/L)
Standard Deviation 40.027
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=13 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=17 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Total Bilirubin up to Month 102
Change at Month 12
|
-45.61 umol/L
Standard Deviation 34.686
|
-55.86 umol/L
Standard Deviation 46.161
|
|
Change From Baseline in Total Bilirubin up to Month 102
Change at Month 36
|
-41.66 umol/L
Standard Deviation 41.309
|
-42.14 umol/L
Standard Deviation 42.841
|
|
Change From Baseline in Total Bilirubin up to Month 102
Change at Month 60
|
-39.71 umol/L
Standard Deviation 37.754
|
-41.78 umol/L
Standard Deviation 38.803
|
|
Change From Baseline in Total Bilirubin up to Month 102
Change at Month 84
|
-47.04 umol/L
Standard Deviation 38.220
|
-46.81 umol/L
Standard Deviation 46.865
|
|
Change From Baseline in Total Bilirubin up to Month 102
Change at Month 102
|
-65.85 umol/L
Standard Deviation 57.731
|
-96.16 umol/L
Standard Deviation 63.521
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Indirect Bilirubin at Week 24
Baseline
|
85.74 umol/L
Standard Deviation 52.881
|
86.64 umol/L
Standard Deviation 53.717
|
|
Change From Baseline in Indirect Bilirubin at Week 24
Change at Week 24
|
-36.69 umol/L
Standard Deviation 31.979
|
-53.99 umol/L
Standard Deviation 40.081
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=12 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=17 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Indirect Bilirubin up to Month 102
Change at Month 102
|
-68.42 umol/L
Standard Deviation 58.135
|
-95.69 umol/L
Standard Deviation 60.128
|
|
Change From Baseline in Indirect Bilirubin up to Month 102
Change at Month 12
|
-46.32 umol/L
Standard Deviation 35.996
|
-54.92 umol/L
Standard Deviation 45.237
|
|
Change From Baseline in Indirect Bilirubin up to Month 102
Change at Month 36
|
-41.17 umol/L
Standard Deviation 42.994
|
-45.81 umol/L
Standard Deviation 42.396
|
|
Change From Baseline in Indirect Bilirubin up to Month 102
Change at Month 60
|
-39.46 umol/L
Standard Deviation 39.129
|
-45.04 umol/L
Standard Deviation 39.308
|
|
Change From Baseline in Indirect Bilirubin up to Month 102
Change at Month 84
|
-47.52 umol/L
Standard Deviation 39.990
|
-49.57 umol/L
Standard Deviation 46.674
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Erythropoietin (EPO) at Week 24
Baseline
|
85.45 international units per liter (IU/L)
Standard Deviation 159.409
|
60.90 international units per liter (IU/L)
Standard Deviation 19.519
|
|
Change From Baseline in Erythropoietin (EPO) at Week 24
Change at Week 24
|
-7.11 international units per liter (IU/L)
Standard Deviation 34.754
|
-12.61 international units per liter (IU/L)
Standard Deviation 26.596
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 18, 24, and 30Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=13 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=17 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in (EPO) up to Month 30
Change at Month 18
|
1.17 IU/L
Standard Deviation 33.991
|
-18.89 IU/L
Standard Deviation 24.148
|
|
Change From Baseline in (EPO) up to Month 30
Change at Month 12
|
10.17 IU/L
Standard Deviation 38.685
|
-11.09 IU/L
Standard Deviation 38.484
|
|
Change From Baseline in (EPO) up to Month 30
Change at Month 24
|
-15.50 IU/L
Standard Deviation 28.899
|
-26.46 IU/L
Standard Deviation 20.701
|
|
Change From Baseline in (EPO) up to Month 30
Change at Month 30
|
-12.01 IU/L
Standard Deviation 15.495
|
-21.80 IU/L
Standard Deviation 24.400
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=6 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=6 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Hepcidin at Week 24
Baseline
|
9471.7 nanograms per liter (ng/L)
Standard Deviation 9501.70
|
10708.3 nanograms per liter (ng/L)
Standard Deviation 10109.53
|
|
Change From Baseline in Hepcidin at Week 24
Change at Week 24
|
-1011.7 nanograms per liter (ng/L)
Standard Deviation 6156.16
|
-4684.0 nanograms per liter (ng/L)
Standard Deviation 5631.56
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 18, 24, and 30Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=5 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Hepcidin up to Month 30
Change at Month 12
|
-2755.0 ng/L
Standard Deviation 12485.25
|
-6606.0 ng/L
Standard Deviation 8980.10
|
|
Change From Baseline in Hepcidin up to Month 30
Change at Month 18
|
3900.0 ng/L
Standard Deviation 3334.29
|
-1633.3 ng/L
Standard Deviation 864.08
|
|
Change From Baseline in Hepcidin up to Month 30
Change at Month 24
|
7076.7 ng/L
Standard Deviation 2918.17
|
-7930.0 ng/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
|
Change From Baseline in Hepcidin up to Month 30
Change at Month 30
|
4400.0 ng/L
Standard Deviation 3450.93
|
-3650.0 ng/L
Standard Deviation NA
Standard deviation was not estimable for a single participant.
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=27 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=25 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Ferritin at Week 24
Baseline
|
857.667 micrograms per liter (ug/L)
Standard Deviation 681.0690
|
868.600 micrograms per liter (ug/L)
Standard Deviation 492.1219
|
|
Change From Baseline in Ferritin at Week 24
Change at Week 24
|
60.333 micrograms per liter (ug/L)
Standard Deviation 406.5114
|
-7.286 micrograms per liter (ug/L)
Standard Deviation 232.9322
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=13 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=17 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Ferritin up to Month 102
Change at Month 12
|
-20.692 ug/L
Standard Deviation 207.6064
|
2.265 ug/L
Standard Deviation 196.0776
|
|
Change From Baseline in Ferritin up to Month 102
Change at Month 36
|
-25.286 ug/L
Standard Deviation 396.5967
|
-136.150 ug/L
Standard Deviation 136.3716
|
|
Change From Baseline in Ferritin up to Month 102
Change at Month 60
|
-162.667 ug/L
Standard Deviation 615.9044
|
-279.944 ug/L
Standard Deviation 220.8130
|
|
Change From Baseline in Ferritin up to Month 102
Change at Month 84
|
136.000 ug/L
Standard Deviation 163.1086
|
-385.722 ug/L
Standard Deviation 285.6371
|
|
Change From Baseline in Ferritin up to Month 102
Change at Month 102
|
193.333 ug/L
Standard Deviation 80.7548
|
-361.000 ug/L
Standard Deviation 163.9909
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data. Number analyzed is the number of participants with evaluable data at the given time-point.
Transferrin saturation is the ratio of serum iron to iron-binding capacity. Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased transferrin saturation values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=21 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=24 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Transferrin Saturation at Week 24
Baseline
|
0.501 fraction of 1
Standard Deviation 0.2374
|
0.643 fraction of 1
Standard Deviation 0.2188
|
|
Change From Baseline in Transferrin Saturation at Week 24
Change at Week 24
|
-0.055 fraction of 1
Standard Deviation 0.1490
|
-0.036 fraction of 1
Standard Deviation 0.1819
|
SECONDARY outcome
Timeframe: Baseline, Months 12, 36, 60, 84, and 102Population: The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.
Transferrin saturation is the ratio of serum iron to iron-binding capacity. Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased transferrin saturation values indicate improvement.
Outcome measures
| Measure |
AG-348 50 mg BID
n=10 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=15 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Change From Baseline in Transferrin Saturation up to Month 102
Change at Month 36
|
-0.074 fraction of 1
Standard Deviation 0.3472
|
-0.067 fraction of 1
Standard Deviation 0.2666
|
|
Change From Baseline in Transferrin Saturation up to Month 102
Change at Month 12
|
-0.039 fraction of 1
Standard Deviation 0.1999
|
-0.034 fraction of 1
Standard Deviation 0.2431
|
|
Change From Baseline in Transferrin Saturation up to Month 102
Change at Month 60
|
0.060 fraction of 1
Standard Deviation 0.2128
|
-0.031 fraction of 1
Standard Deviation 0.1483
|
|
Change From Baseline in Transferrin Saturation up to Month 102
Change at Month 84
|
-0.190 fraction of 1
Standard Deviation 0.2176
|
0.056 fraction of 1
Standard Deviation 0.1319
|
|
Change From Baseline in Transferrin Saturation up to Month 102
Change at Month 102
|
-0.207 fraction of 1
Standard Deviation 0.4200
|
0.117 fraction of 1
Standard Deviation 0.3150
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15Population: The Pharmacokinetic Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess pharmacokinetic parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Outcome measures
| Measure |
AG-348 50 mg BID
n=5 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=7 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) for AG-348 and Its Metabolite AGI-8702
Day 1: AG-348
|
3287 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 20.9
|
27930 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 38.1
|
|
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) for AG-348 and Its Metabolite AGI-8702
Day 15: AG-348
|
3609 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 38.2
|
11610 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 11.3
|
|
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) for AG-348 and Its Metabolite AGI-8702
Day 1: AGI-8702
|
235.6 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 32.6
|
2637 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 34.9
|
|
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) for AG-348 and Its Metabolite AGI-8702
Day 15: AGI-8702
|
425.8 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 21.8
|
2235 nanograms*hours per milliliter(hr*ng/mL)
Geometric Coefficient of Variation 19.4
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15Population: The Pharmacokinetic Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess pharmacokinetic parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Outcome measures
| Measure |
AG-348 50 mg BID
n=5 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=7 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702
Day 1: AG-348
|
870.0 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 9.2
|
7606 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 41.8
|
|
Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702
Day 15: AG-348
|
943.4 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 30.7
|
5259 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 35.6
|
|
Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702
Day 1: AGI-8702
|
41.03 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 43.6
|
414.7 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 35.6
|
|
Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702
Day 15: AGI-8702
|
71.94 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 22.0
|
533.7 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25.6
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15Population: The Pharmacokinetic Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess pharmacokinetic parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Outcome measures
| Measure |
AG-348 50 mg BID
n=5 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=7 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702
Day 1: AG-348
|
1.92 hour (hr)
Interval 0.97 to 2.03
|
1.97 hour (hr)
Interval 1.0 to 2.08
|
|
Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702
Day 15: AG-348
|
1.00 hour (hr)
Interval 0.97 to 1.9
|
1.00 hour (hr)
Interval 0.42 to 2.0
|
|
Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702
Day 1: AGI-8702
|
2.00 hour (hr)
Interval 1.92 to 2.03
|
1.97 hour (hr)
Interval 1.0 to 2.13
|
|
Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702
Day 15: AGI-8702
|
2.00 hour (hr)
Interval 1.95 to 4.0
|
1.00 hour (hr)
Interval 0.93 to 4.0
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15Population: The Pharmacokinetic Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess pharmacokinetic parameters. Number analyzed is the number of participants with evaluable data at the given time-point.
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Outcome measures
| Measure |
AG-348 50 mg BID
n=5 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=7 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Apparent Clearance at Steady-State (Clss/F) for AG-348 and Its Metabolite AGI-8702
Day 15: AG-348
|
12.27 liter per hour (L/hr)
Geometric Coefficient of Variation 40.3
|
25.31 liter per hour (L/hr)
Geometric Coefficient of Variation 11.7
|
|
Apparent Clearance at Steady-State (Clss/F) for AG-348 and Its Metabolite AGI-8702
Day 15: AGI-8702
|
91.50 liter per hour (L/hr)
Geometric Coefficient of Variation 31.0
|
128.2 liter per hour (L/hr)
Geometric Coefficient of Variation 18.8
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1Population: The Pharmacodynamic (PD) Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess PD parameters. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Outcome measures
| Measure |
AG-348 50 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=6 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Maximum Change From Baseline Response Value Over 12 Hours Post-dose (BRmax) for Adenosine Triphosphate (ATP)
|
16.50 microgram per milliliter (µg/mL)
Standard Deviation 11.790
|
20.67 microgram per milliliter (µg/mL)
Standard Deviation 6.8896
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15Population: The PD Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess PD parameters. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Outcome measures
| Measure |
AG-348 50 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
Maximum Change From Baseline Response Value Over 8 Hours Post-dose at Steady State (BRmax ss) for ATP
|
1.500 µg/mL
Standard Deviation 31.032
|
45.50 µg/mL
Standard Deviation 60.995
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1Population: The PD Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess PD parameters. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Outcome measures
| Measure |
AG-348 50 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=7 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
BRmax for 2,3 - Diphosphoglycerate (2,3-DPG)
|
42.25 µg/mL
Standard Deviation 38.836
|
59.57 µg/mL
Standard Deviation 58.569
|
SECONDARY outcome
Timeframe: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15Population: The PD Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess PD parameters. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Outcome measures
| Measure |
AG-348 50 mg BID
n=4 Participants
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
AG-348 300 mg BID
n=5 Participants
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
|
|---|---|---|
|
BRmax ss for 2,3-DPG
|
-65.50 µg/mL
Standard Deviation 69.745
|
8.200 µg/mL
Standard Deviation 195.13
|
Adverse Events
AG-348 50 mg BID (Core Period+ Extension Period)
Serious events: 12 serious events
Other events: 27 other events
Deaths: 0 deaths
AG-348 300 mg BID (Core Period + Extension Period)
Serious events: 7 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AG-348 50 mg BID (Core Period+ Extension Period)
n=27 participants at risk
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID, for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
|
AG-348 300 mg BID (Core Period + Extension Period)
n=25 participants at risk
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID, for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.
|
|---|---|---|
|
Infections and infestations
Pharyngitis
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Influenza
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Hepatobiliary disorders
Cholelithiasis
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Gastroenteritis clostridial
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Gastroenteritis viral
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Infected bite
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Suspected COVID-19
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Colitis
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Psychiatric disorders
Anxiety
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Psychiatric disorders
Depression
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Psychiatric disorders
Initial insomnia
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Renal and urinary disorders
Acute kidney injury
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Renal and urinary disorders
Nephrolithiasis
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Fracture delayed union
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Nervous system disorders
Headache
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Reproductive system and breast disorders
Endometriosis
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
Other adverse events
| Measure |
AG-348 50 mg BID (Core Period+ Extension Period)
n=27 participants at risk
Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID, for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
|
AG-348 300 mg BID (Core Period + Extension Period)
n=25 participants at risk
Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID, for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
44.4%
12/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
48.0%
12/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
32.0%
8/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Diarrhoea
|
22.2%
6/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
24.0%
6/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Abdominal pain
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Nervous system disorders
Headache
|
48.1%
13/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
60.0%
15/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Nervous system disorders
Dizziness
|
18.5%
5/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.2%
6/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
28.0%
7/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.8%
4/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
14.8%
4/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
24.0%
6/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Influenza
|
25.9%
7/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Gastroenteritis
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Sinusitis
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Upper respiratory tract infection
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Psychiatric disorders
Insomnia
|
25.9%
7/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
64.0%
16/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.8%
4/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
22.2%
6/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.8%
4/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Fatigue
|
25.9%
7/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
32.0%
8/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Pyrexia
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
36.0%
9/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Chest discomfort
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
24.0%
6/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Asthenia
|
14.8%
4/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Vascular disorders
Hot flush
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
28.0%
7/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Vascular disorders
Flushing
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
18.5%
5/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Cardiac disorders
Palpitations
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Nasopharyngitis
|
40.7%
11/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
36.0%
9/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
COVID-19
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
20.0%
5/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Urinary tract infection
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Influenza like illness
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Pain
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Nervous system disorders
Paraesthesia
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Nervous system disorders
Anosmia
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Investigations
Alanine aminotransferase increased
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Investigations
Haemoglobin decreased
|
11.1%
3/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Investigations
Blood bilirubin increased
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Investigations
Blood triglycerides increased
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Investigations
Haemoglobin increased
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Psychiatric disorders
Initial insomnia
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Psychiatric disorders
Middle insomnia
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Blood and lymphatic system disorders
Anaemia
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
16.0%
4/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Vascular disorders
Hypertension
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Vascular disorders
Superficial vein thrombosis
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Hepatobiliary disorders
Ocular icterus
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Gastrointestinal disorders
Dry Mouth
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Chills
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
4.0%
1/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
General disorders
Peripheral Swelling
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Rhinitis
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Limb Discomfort
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Nervous system disorders
Taste Disorder
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Psychiatric disorders
Anxiety
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Reproductive system and breast disorders
Breast Enlargement
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Reproductive system and breast disorders
Heavy menstrual bleeding
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Ear and labyrinth disorders
Tinnitus
|
3.7%
1/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Ear and labyrinth disorders
Ear congestion
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
12.0%
3/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Eye disorders
Vision blurred
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Injury, poisoning and procedural complications
Scratch
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Investigations
Aspartate aminotransferase increased
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.4%
2/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
0.00%
0/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/27 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
8.0%
2/25 • Up to Month 102
The Safety Analysis Set included all participants who had received at least one dose of study drug. As pre-specified in Protocol, cumulative safety data for Core period and Extension period was reported.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The information obtained from the clinical study will be used towards the development of AG-348 and may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or consultants as required.
- Publication restrictions are in place
Restriction type: OTHER