Trial Outcomes & Findings for Study to Assess the Blood Concentrations and Actions of Recombinant Human Parathyroid Hormone (rhPTH [1-84]) When Given Once and Twice Daily to Participants With Hypoparathyroidism (NCT NCT02781844)
NCT ID: NCT02781844
Last Updated: 2021-05-25
Results Overview
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. Tmax of baseline adjusted rhPTH(1-84) was reported. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
34 participants
Primary outcome timeframe
QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose ; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dose
Results posted on
2021-05-25
Participant Flow
This study was conducted in North America and Europe between 04 March 2017 (first participant first visit) to 08 March 2019 (last participant last visit).
A total of 34 participants were enrolled and 33 completed the study. The study consisted of two treatment periods (Treatment period I and II) with four cohorts. Cohort I included Sequence AB and BA. Cohort II included Sequence CB and BC. Cohort III included Sequence DE and ED, Cohort IV included Sequence FE and EF.
Participant milestones
| Measure |
Cohort I: Treatment A / B
Participants received 25 microgram (mcg) rhPTH(1-84) twice daily (BID) with no calcium for treatment period 1 and 100 mcg rhPTH(1-84) once daily (QD) with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of greater than or equal to (\>=) 5 days but less than or equal to (\<=) 30 days between the administration of 25 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort I: Treatment B / A
Participants received 100 mcg rhPTH(1-84) QD with no calcium for treatment period 1 and 25 mcg rhPTH(1-84) BID with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 25 mcg BID rhPTH(1-84).
|
Cohort II: Treatment C / B
Participants received 50 mcg rhPTH(1-84) BID with no calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 50 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort II: Treatment B / C
Participants received 100 mcg rhPTH(1-84) QD with no calcium for treatment period 1 and 50 mcg rhPTH(1-84) BID with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 50 mcg BID rhPTH(1-84).
|
Cohort III: Treatment D / E
Participants received 25 mcg rhPTH(1-84) BID with calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 25 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort III: Treatment E / D
Participants received 100 mcg rhPTH(1-84) QD with calcium for treatment period 1 and 25 mcg rhPTH(1-84) BID with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 25 mcg BID rhPTH(1-84).
|
Cohort IV: Treatment F / E
Participants received 50 mcg rhPTH(1-84) BID with calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 50 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort IV: Treatment E / F
Participants received 100 mcg rhPTH(1-84) QD with calcium for treatment period 1 and 50 mcg rhPTH(1-84) BID with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 50 mcg BID rhPTH(1-84).
|
|---|---|---|---|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
5
|
4
|
4
|
4
|
4
|
5
|
4
|
4
|
|
Treatment Period 1
COMPLETED
|
5
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Treatment Period 2
STARTED
|
5
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 2
COMPLETED
|
5
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort I: Treatment A / B
Participants received 25 microgram (mcg) rhPTH(1-84) twice daily (BID) with no calcium for treatment period 1 and 100 mcg rhPTH(1-84) once daily (QD) with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of greater than or equal to (\>=) 5 days but less than or equal to (\<=) 30 days between the administration of 25 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort I: Treatment B / A
Participants received 100 mcg rhPTH(1-84) QD with no calcium for treatment period 1 and 25 mcg rhPTH(1-84) BID with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 25 mcg BID rhPTH(1-84).
|
Cohort II: Treatment C / B
Participants received 50 mcg rhPTH(1-84) BID with no calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 50 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort II: Treatment B / C
Participants received 100 mcg rhPTH(1-84) QD with no calcium for treatment period 1 and 50 mcg rhPTH(1-84) BID with no calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 50 mcg BID rhPTH(1-84).
|
Cohort III: Treatment D / E
Participants received 25 mcg rhPTH(1-84) BID with calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 25 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort III: Treatment E / D
Participants received 100 mcg rhPTH(1-84) QD with calcium for treatment period 1 and 25 mcg rhPTH(1-84) BID with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 25 mcg BID rhPTH(1-84).
|
Cohort IV: Treatment F / E
Participants received 50 mcg rhPTH(1-84) BID with calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 50 mcg BID and 100 mcg QD rhPTH(1-84).
|
Cohort IV: Treatment E / F
Participants received 100 mcg rhPTH(1-84) QD with calcium for treatment period 1 and 50 mcg rhPTH(1-84) BID with calcium for treatment period 2 in the morning on Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of 100 mcg QD and 50 mcg BID rhPTH(1-84).
|
|---|---|---|---|---|---|---|---|---|
|
Treatment Period 1
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Study to Assess the Blood Concentrations and Actions of Recombinant Human Parathyroid Hormone (rhPTH [1-84]) When Given Once and Twice Daily to Participants With Hypoparathyroidism
Baseline characteristics by cohort
| Measure |
Cohort I: Treatment A/B or Treatment B/A
n=9 Participants
Participants received either 25 mcg rhPTH(1-84) BID with no calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with no calcium for treatment period 2; or 100 mcg rhPTH(1-84) QD with no calcium for treatment period 1 and 25 mcg rhPTH(1-84) BID with no calcium for treatment period 2 in the morning of Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of rhPTH(1-84) or the first administration of rhPTH(1-84) in each period for QD or BID dosing, respectively.
|
Cohort II: Treatment C/B or Treatment B/C
n=8 Participants
Participants received either 50 mcg rhPTH(1-84) BID with no calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with no calcium for treatment period 2; or 100 mcg rhPTH(1-84) QD with no calcium for treatment period 1 and 50 mcg rhPTH(1-84) BID with no calcium for treatment period 2 in the morning of Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of rhPTH(1-84) or the first administration of rhPTH(1-84) in each period for QD or BID dosing, respectively.
|
Cohort III: Treatment D/E or Treatment E/D
n=9 Participants
Participants received either 25 mcg rhPTH(1-84) BID with calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with calcium for treatment period 2; or 100 mcg rhPTH(1-84) QD with calcium for treatment period 1 and 25 mcg rhPTH(1-84) BID with calcium for treatment period 2 in the morning of Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of rhPTH(1-84) or the first administration of rhPTH(1-84) in each period for QD or BID dosing, respectively.
|
Cohort IV: Treatment F/E or Treatment E/F
n=8 Participants
Participants receive either 50 mcg rhPTH(1-84) BID with calcium for treatment period 1 and 100 mcg rhPTH(1-84) QD with calcium for treatment period 2; or 100 mcg rhPTH(1-84) QD with calcium for treatment period 1 and 50 mcg rhPTH(1-84) BID with calcium for treatment period 2 in the morning of Day 1 of respective treatment periods. The 2 treatment periods were separated by a washout period of \> or = 5 days but \< or = 30 days between the administration of rhPTH(1-84) or the first administration of rhPTH(1-84) in each period for QD or BID dosing, respectively.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
42.6 Years
STANDARD_DEVIATION 9.06 • n=99 Participants
|
48.9 Years
STANDARD_DEVIATION 13.48 • n=107 Participants
|
52.4 Years
STANDARD_DEVIATION 13.31 • n=206 Participants
|
45.8 Years
STANDARD_DEVIATION 9.02 • n=7 Participants
|
47.4 Years
STANDARD_DEVIATION 11.54 • n=31 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
30 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
34 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
32 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose ; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dosePopulation: Pharmacokinetic (PK) analysis set consisted of all enrolled participants who did not have major protocol violations that affected the validity of the PK results, received at least 1 dose of rhPTH(1-84) and had at least 1 evaluable postdose PK concentration value available for 1 dose regimen.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. Tmax of baseline adjusted rhPTH(1-84) was reported. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Time of Maximum Observed Concentration (Cmax) During a Dosing Interval (Tmax) of Baseline Adjusted rhPTH(1-84)
|
7.108 hours
Interval 0.18 to 14.07
|
7.083 hours
Interval 0.17 to 13.5
|
0.333 hours
Interval 0.17 to 4.17
|
1.000 hours
Interval 0.15 to 14.0
|
12.167 hours
Interval 0.17 to 13.5
|
0.667 hours
Interval 0.12 to 4.0
|
PRIMARY outcome
Timeframe: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dosePopulation: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. Cmax of baseline adjusted rhPTH(1-84) was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Baseline Adjusted rhPTH(1-84)
|
136.9 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 50.9
|
213.6 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 51.6
|
339.1 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 137.8
|
120.9 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 83.6
|
100.5 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 106.2
|
240.8 picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 69.6
|
PRIMARY outcome
Timeframe: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dosePopulation: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure and at specific category.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUClast of baseline adjsuted plasma rhPTH(1-84) was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=13 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Baseline Adjusted rhPTH(1-84)
|
496.0 hour*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 34.1
|
653.2 hour*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 25.5
|
901.1 hour*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 448.5
|
205.0 hour*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 106.6
|
261.1 hour*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 77.6
|
1044.9 hour*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 58.0
|
PRIMARY outcome
Timeframe: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dosePopulation: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure and at specific category.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUCinf of baseline adjusted rhPTH(1-84) was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=4 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=13 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=3 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=1 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=12 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Curve Extrapolated to Infinity (AUCinf) of Baseline Adjusted rhPTH(1-84)
|
484.8 h*pg/mL
Geometric Coefficient of Variation 48.4
|
677.7 h*pg/mL
Geometric Coefficient of Variation 22.9
|
1567.6 h*pg/mL
Geometric Coefficient of Variation 36.7
|
255.0 h*pg/mL
Geometric Coefficient of Variation 198.3
|
600.8 h*pg/mL
Geometric Coefficient of Variation NA
Geometric CV% cannot be calculated for one single participant. This outcome measure was analyzed only in one participants for cohort IV.
|
1043.5 h*pg/mL
Geometric Coefficient of Variation 50.4
|
PRIMARY outcome
Timeframe: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24 hours post-dosePopulation: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUC0-24 of baseline adjusted rhPTH(1-84) was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=13 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration Curve From Time Zero to 24 Hours Post the First Dose (AUC0-24) of Baseline Adjusted rhPTH(1-84)
|
944.6 h*pg/mL
Geometric Coefficient of Variation 29.9
|
1357.6 h*pg/mL
Geometric Coefficient of Variation 31.3
|
973.7 h*pg/mL
Geometric Coefficient of Variation 334.6
|
577.6 h*pg/mL
Geometric Coefficient of Variation 94.3
|
606.3 h*pg/mL
Geometric Coefficient of Variation 135.3
|
1106.8 h*pg/mL
Geometric Coefficient of Variation 59.3
|
PRIMARY outcome
Timeframe: BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours post-dosePopulation: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUC0-12 of baseline adjusted rhPTH(1-84) was reported. AUC(0-12) was planned, analyzed and reported only in participants who received BID treatment ( Treatment A, Treatment C, Treatment D, Treatment F).
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=8 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=6 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration Curve From Time Zero to 12 Hours Post the First Dose (AUC0-12) of Baseline Adjusted rhPTH(1-84)
|
462.1 h*pg/mL
Geometric Coefficient of Variation 29.9
|
665.2 h*pg/mL
Geometric Coefficient of Variation 42.3
|
298.8 h*pg/mL
Geometric Coefficient of Variation 113.9
|
220.2 h*pg/mL
Geometric Coefficient of Variation 354.7
|
—
|
—
|
PRIMARY outcome
Timeframe: BID: 12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24 hours post-dosePopulation: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. AUC12-24 of baseline adjusted rhPTH(1-84) was reported. AUC(12-24) was planned, analyzed and reported only in participants who received BID treatment ( Treatment A, Treatment C, Treatment D, Treatment F).
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=8 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=6 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration Curve From Time of the Second Dose to 12 Hours Post the Second Dose (AUC12-24) of Baseline Adjusted rhPTH(1-84)
|
479.0 h*pg/mL
Geometric Coefficient of Variation 33.3
|
679.5 h*pg/mL
Geometric Coefficient of Variation 25.5
|
245.2 h*pg/mL
Geometric Coefficient of Variation 93.5
|
323.2 h*pg/mL
Geometric Coefficient of Variation 71.7
|
—
|
—
|
PRIMARY outcome
Timeframe: QD: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12,16 and 24 hours post-dose; BID: Pre-dose,10,20,30 minutes,1,1.5,2,4,8,12 hours,12 hour 10 minutes,12 hour 20 minutes,12 hour 30 minutes,13 hours, 13 hour 30 minutes,14,16,20,22,24,28 and 36 hours post-dosePopulation: PK analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure and at specific category.
Baseline-adjusted rhPTH(1-84) concentrations (participant- and period-specific) were calculated by subtracting baseline endogenous PTH from the raw PTH concentrations. The baseline was defined as premorning-dose endogenous rhPTH(1-84) level on Day 1 for each treatment period. T1/2 of baseline adjusted rhPTH(1-84) was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=4 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=13 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=3 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=1 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=12 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Terminal Half-Life (t1/2) of Baseline Adjusted rhPTH(1-84)
|
1.739 hours
Geometric Coefficient of Variation 39.461
|
2.073 hours
Geometric Coefficient of Variation 38.704
|
1.973 hours
Geometric Coefficient of Variation 42.421
|
1.446 hours
Geometric Coefficient of Variation 62.293
|
1.773 hours
Geometric Coefficient of Variation NA
Geometric CV% cannot be calculated for one single participant. This outcome measure was analyzed only in one participant for cohort IV.
|
2.190 hours
Geometric Coefficient of Variation 38.206
|
PRIMARY outcome
Timeframe: Day -1Population: Pharmacodynamic (PD) analysis set consisted of all enrolled participants who did not have major protocol violations that affected the validity of the PD results, received at least 1 dose of rhPTH(1 84) and had at least 1 evaluable post-dose PD value available for 1 dose regimen.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCabove of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 was reported. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Outcome measures
| Measure |
Cohort I: Treatment A
n=7 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve That is Above the Baseline, From Time 0 to 24 Hours (AUCabove) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Total Calcium
|
2.672 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 1.8280
|
1.190 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 1.3884
|
0.616 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 0.8793
|
0.934 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 0.7920
|
1.890 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 1.7930
|
1.162 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 1.2725
|
|
Area Under the Concentration-Time Curve That is Above the Baseline, From Time 0 to 24 Hours (AUCabove) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Calcium (Albumin-Corrected)
|
2.714 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 1.5038
|
1.189 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 1.5482
|
0.701 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 0.9478
|
0.802 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 0.7234
|
1.470 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 1.7843
|
0.791 hour*millimoles per Liter (h*mmol/L)
Standard Deviation 0.8162
|
PRIMARY outcome
Timeframe: Day -1Population: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCbelow of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=7 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve That is Below the Baseline, From Time 0 to 24 Hours (AUCbelow) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Calcium (Albumin-Corrected)
|
0.283 h*mmol/L
Standard Deviation 0.5173
|
0.380 h*mmol/L
Standard Deviation 0.3621
|
1.291 h*mmol/L
Standard Deviation 1.8883
|
0.637 h*mmol/L
Standard Deviation 1.0314
|
0.434 h*mmol/L
Standard Deviation 0.6786
|
0.816 h*mmol/L
Standard Deviation 0.9874
|
|
Area Under the Concentration-Time Curve That is Below the Baseline, From Time 0 to 24 Hours (AUCbelow) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Total Calcium
|
0.238 h*mmol/L
Standard Deviation 0.4379
|
0.394 h*mmol/L
Standard Deviation 0.3259
|
1.570 h*mmol/L
Standard Deviation 1.9043
|
0.639 h*mmol/L
Standard Deviation 0.9601
|
0.515 h*mmol/L
Standard Deviation 0.6182
|
0.998 h*mmol/L
Standard Deviation 1.3267
|
PRIMARY outcome
Timeframe: Day -1Population: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. TEmax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 were reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=7 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Time to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Calcium (Albumin-Corrected)
|
8.000 hours
Interval 4.0 to 16.52
|
13.583 hours
Interval 8.05 to 16.0
|
6.000 hours
Interval 0.0 to 13.8
|
7.317 hours
Interval 3.97 to 23.92
|
9.250 hours
Interval 1.67 to 24.07
|
13.692 hours
Interval 0.0 to 24.73
|
|
Time to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Total Calcium
|
8.000 hours
Interval 4.0 to 16.52
|
12.100 hours
Interval 0.0 to 25.47
|
4.200 hours
Interval 0.0 to 16.25
|
5.208 hours
Interval 1.67 to 23.92
|
5.367 hours
Interval 1.67 to 24.07
|
13.692 hours
Interval 0.0 to 24.73
|
PRIMARY outcome
Timeframe: Day -1Population: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. Emax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day -1 were reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=7 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Calcium (Albumin-Corrected)
|
0.284 millimoles/Liter (mmol/L)
Standard Deviation 0.1495
|
0.110 millimoles/Liter (mmol/L)
Standard Deviation 0.1098
|
0.102 millimoles/Liter (mmol/L)
Standard Deviation 0.0892
|
0.098 millimoles/Liter (mmol/L)
Standard Deviation 0.0539
|
0.148 millimoles/Liter (mmol/L)
Standard Deviation 0.1398
|
0.107 millimoles/Liter (mmol/L)
Standard Deviation 0.0783
|
|
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day -1
Total Calcium
|
0.273 millimoles/Liter (mmol/L)
Standard Deviation 0.1874
|
0.116 millimoles/Liter (mmol/L)
Standard Deviation 0.1066
|
0.100 millimoles/Liter (mmol/L)
Standard Deviation 0.0921
|
0.121 millimoles/Liter (mmol/L)
Standard Deviation 0.0690
|
0.197 millimoles/Liter (mmol/L)
Standard Deviation 0.1465
|
0.127 millimoles/Liter (mmol/L)
Standard Deviation 0.0947
|
PRIMARY outcome
Timeframe: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dosePopulation: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCabove of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 were reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve That is Above the Baseline, From Time 0 to 24 Hours (AUCabove) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Calcium (albumin-corrected)
|
1.222 h*mmol/L
Standard Deviation 1.2757
|
1.084 h*mmol/L
Standard Deviation 0.8887
|
1.645 h*mmol/L
Standard Deviation 1.1038
|
2.860 h*mmol/L
Standard Deviation 4.1108
|
1.468 h*mmol/L
Standard Deviation 1.5533
|
2.610 h*mmol/L
Standard Deviation 1.5520
|
|
Area Under the Concentration-Time Curve That is Above the Baseline, From Time 0 to 24 Hours (AUCabove) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Total Calcium
|
1.060 h*mmol/L
Standard Deviation 1.0398
|
0.715 h*mmol/L
Standard Deviation 0.5001
|
1.769 h*mmol/L
Standard Deviation 1.3569
|
3.259 h*mmol/L
Standard Deviation 4.6635
|
1.540 h*mmol/L
Standard Deviation 1.6227
|
2.456 h*mmol/L
Standard Deviation 1.4576
|
PRIMARY outcome
Timeframe: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dosePopulation: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. AUCbelow of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration-Time Curve That is Below the Baseline, From Time 0 to 24 Hours (AUCbelow) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Calcium (Albumin-Corrected)
|
1.085 h*mmol/L
Standard Deviation 1.1804
|
0.393 h*mmol/L
Standard Deviation 0.6320
|
0.197 h*mmol/L
Standard Deviation 0.2940
|
0.309 h*mmol/L
Standard Deviation 0.5883
|
0.548 h*mmol/L
Standard Deviation 0.6416
|
0.316 h*mmol/L
Standard Deviation 0.5706
|
|
Area Under the Concentration-Time Curve That is Below the Baseline, From Time 0 to 24 Hours (AUCbelow) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Total Calcium
|
0.944 h*mmol/L
Standard Deviation 1.1352
|
0.362 h*mmol/L
Standard Deviation 0.3115
|
0.320 h*mmol/L
Standard Deviation 0.5456
|
0.273 h*mmol/L
Standard Deviation 0.4174
|
0.601 h*mmol/L
Standard Deviation 0.6863
|
0.437 h*mmol/L
Standard Deviation 0.7870
|
PRIMARY outcome
Timeframe: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dosePopulation: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. TEmax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 were reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Time to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Calcium (albumin-corrected)
|
11.667 hours
Interval 0.0 to 24.13
|
18.000 hours
Interval 4.0 to 22.0
|
8.017 hours
Interval 1.5 to 24.02
|
18.000 hours
Interval 8.0 to 36.0
|
17.000 hours
Interval 8.1 to 20.0
|
9.075 hours
Interval 0.0 to 16.2
|
|
Time to Maximum Effect (TEmax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Total Calcium
|
21.108 hours
Interval 0.0 to 28.02
|
10.000 hours
Interval 1.5 to 22.0
|
9.917 hours
Interval 1.5 to 24.18
|
13.508 hours
Interval 8.0 to 20.0
|
16.000 hours
Interval 8.1 to 36.02
|
8.092 hours
Interval 0.0 to 16.2
|
PRIMARY outcome
Timeframe: Day1- QD: Pre-dose up to 24 hours post dose, Day2- BID: Pre-dose up to 36 hours post dosePopulation: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Baseline-adjusted concentrations calculated by subtracting the appropriate baseline values from the raw concentrations at each time point. Emax of baseline-adjusted serum calcium (albumin-corrected) and total calcium (calcium \[uncorrected\]) concentrations on Day 1/Day 2 were reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Calcium (albumin-corrected)
|
0.146 mmol/L
Standard Deviation 0.1031
|
0.120 mmol/L
Standard Deviation 0.0746
|
0.173 mmol/L
Standard Deviation 0.0825
|
0.205 mmol/L
Standard Deviation 0.1999
|
0.160 mmol/L
Standard Deviation 0.0994
|
0.216 mmol/L
Standard Deviation 0.1252
|
|
Maximum Effect (Emax) of Baseline-Adjusted Serum Calcium Concentrations on Day 1/Day 2
Total Calcium
|
0.139 mmol/L
Standard Deviation 0.1029
|
0.103 mmol/L
Standard Deviation 0.0489
|
0.183 mmol/L
Standard Deviation 0.0993
|
0.243 mmol/L
Standard Deviation 0.2247
|
0.183 mmol/L
Standard Deviation 0.0873
|
0.207 mmol/L
Standard Deviation 0.1025
|
PRIMARY outcome
Timeframe: Day -1Population: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Total amount of urinary calcium excretion to total relative amount of creatinine over 24 hours by Day -1 was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=13 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Total Amount of Urinary Calcium Excretion to Total Relative Amount of Creatinine Over 24 Hours by Day -1
|
0.806 mmol/mmol
Standard Deviation 0.2284
|
0.836 mmol/mmol
Standard Deviation 0.3020
|
0.727 mmol/mmol
Standard Deviation 0.2859
|
0.874 mmol/mmol
Standard Deviation 0.2670
|
0.855 mmol/mmol
Standard Deviation 0.2858
|
0.807 mmol/mmol
Standard Deviation 0.2764
|
PRIMARY outcome
Timeframe: Day 1- QD: Pre-dose up to 24 hours post dose, Day 2- BID: Pre-dose up to 24 hours post dosePopulation: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Total amount of urinary calcium excretion to total relative amount of creatinine over 24 hours by Day 1/ Day 2 was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=7 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Total Amount of Urinary Calcium Excretion to Total Relative Amount of Creatinine Over 24 Hours by Day 1/ Day 2
|
0.401 millimoles Per millimoles (mmol/mmol)
Standard Deviation 0.1665
|
0.394 millimoles Per millimoles (mmol/mmol)
Standard Deviation 0.1278
|
0.475 millimoles Per millimoles (mmol/mmol)
Standard Deviation 0.1725
|
0.678 millimoles Per millimoles (mmol/mmol)
Standard Deviation 0.2123
|
0.673 millimoles Per millimoles (mmol/mmol)
Standard Deviation 0.2377
|
0.691 millimoles Per millimoles (mmol/mmol)
Standard Deviation 0.2364
|
PRIMARY outcome
Timeframe: Day -1Population: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Total urinary excretion of calcium over 24 Hours by Day -1 was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=15 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=13 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Total Urinary Excretion of Calcium Over 24 Hours by Day -1
|
9.348 mmol
Standard Deviation 3.9559
|
10.239 mmol
Standard Deviation 3.7130
|
8.880 mmol
Standard Deviation 3.7407
|
10.831 mmol
Standard Deviation 2.8306
|
10.735 mmol
Standard Deviation 2.9224
|
9.717 mmol
Standard Deviation 2.9354
|
PRIMARY outcome
Timeframe: Day 1- QD: Pre-dose up to 24 hours post dose, Day 2- BID: Pre-dose up to 24 hours post dosePopulation: PD analysis set. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Total urinary excretion of calcium over 24 hours by Day1/Day 2 was reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=7 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=7 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=6 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=14 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Total Urinary Excretion of Calcium Over 24 Hours by Day 1/ Day 2
|
4.904 mmol
Standard Deviation 1.9684
|
5.137 mmol
Standard Deviation 1.9800
|
6.037 mmol
Standard Deviation 2.5353
|
7.440 mmol
Standard Deviation 2.5379
|
8.813 mmol
Standard Deviation 2.8213
|
7.928 mmol
Standard Deviation 2.3159
|
SECONDARY outcome
Timeframe: From signing of informed consent up to follow up (up to Day 182)Population: Safety analysis set included enrolled participants who received at least 1 dose of rhPTH(1 84).
An AE that occured during the study was considered a TEAE if it had a start date/time on or after the first dose of investigational product or if it had a start date before the date of the first dose of investigational product, but increased in severity on or after the date/time of the first dose of investigational product. Number of participants with TEAE's were reported.
Outcome measures
| Measure |
Cohort I: Treatment A
n=9 Participants
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=17 Participants
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 Participants
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=8 Participants
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=17 Participants
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE's)
|
3 Participants
|
1 Participants
|
4 Participants
|
5 Participants
|
3 Participants
|
7 Participants
|
Adverse Events
Cohort I: Treatment A
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort II: Treatment C
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort I+II: Treatment B
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort III: Treatment D
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Cohort IV: Treatment F
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort III + IV: Treatment E
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort I: Treatment A
n=9 participants at risk
Participants received 25 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in cohort I.
|
Cohort II: Treatment C
n=8 participants at risk
Participants received 50 mcg rhPTH(1-84) BID with no calcium in the morning on Day 1 of respective treatment period in Cohort II.
|
Cohort I+II: Treatment B
n=17 participants at risk
Participants received 100 mcg rhPTH(1-84) QD with no calcium in both cohort I and II in the morning on Day 1 of respective treatment period.
|
Cohort III: Treatment D
n=8 participants at risk
Participants received 25 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort III.
|
Cohort IV: Treatment F
n=8 participants at risk
Participants received 50 mcg rhPTH(1-84) BID with calcium in the morning on Day 1 of respective treatment period in Cohort IV.
|
Cohort III + IV: Treatment E
n=17 participants at risk
Participants received 100 mcg rhPTH(1-84) QD with calcium in both cohort III and IV in the morning on Day 1 of respective treatment period.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
17.6%
3/17 • Number of events 3 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
25.0%
2/8 • Number of events 2 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Gastrointestinal disorders
Faeces soft
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Gastrointestinal disorders
Mouth ulceration
|
11.1%
1/9 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
17.6%
3/17 • Number of events 3 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
11.8%
2/17 • Number of events 2 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Nervous system disorders
Headache
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 5 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
17.6%
3/17 • Number of events 4 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Nervous system disorders
Hypoaesthesia
|
11.1%
1/9 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Nervous system disorders
Syncope
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
General disorders
Catheter site pain
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
General disorders
Fatigue
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
General disorders
Feeling hot
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
General disorders
Injection site pain
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
General disorders
Malaise
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
General disorders
Medical device site ulcer
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Vascular disorders
Hot flush
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
25.0%
2/8 • Number of events 2 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
11.8%
2/17 • Number of events 2 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Cardiac disorders
Palpitations
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Investigations
Blood calcium decreased
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Investigations
Haematocrit decreased
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
11.1%
1/9 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Infections and infestations
Viral pharyngitis
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
12.5%
1/8 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
|
Psychiatric disorders
Depression
|
0.00%
0/9 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/17 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
0.00%
0/8 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
5.9%
1/17 • Number of events 1 • From signing of informed consent up to follow up (up to Day 182)
One participant during the washout out period following the 100 mcg QD dosing treatment period with calcium supplement in cohort III withdrew from the study and considered only in combined arm (Cohort III + IV).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER