Trial Outcomes & Findings for Metformin as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease (NCT NCT02656017)
NCT ID: NCT02656017
Last Updated: 2022-08-09
Results Overview
GSRS is a widely used, validated 15-item questionnaire used to assess GI symptom burden (minimum, maximum: 1, 7, where higher mean score is worse outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
97 participants
Primary outcome timeframe
Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
Results posted on
2022-08-09
Participant Flow
Participant milestones
| Measure |
Metformin
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Overall Study
STARTED
|
49
|
48
|
|
Overall Study
COMPLETED
|
40
|
42
|
|
Overall Study
NOT COMPLETED
|
9
|
6
|
Reasons for withdrawal
| Measure |
Metformin
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Overall Study
Study burden
|
3
|
3
|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Unable/unwilling to take study medication
|
2
|
1
|
|
Overall Study
Began Tolvaptan
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Two participants are missing results.
Baseline characteristics by cohort
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
Total
n=97 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=97 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
49 Participants
n=49 Participants
|
48 Participants
n=48 Participants
|
97 Participants
n=97 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=97 Participants
|
|
Age, Continuous
|
41.8 years
STANDARD_DEVIATION 10.4 • n=49 Participants
|
42.1 years
STANDARD_DEVIATION 10.1 • n=48 Participants
|
41.9 years
STANDARD_DEVIATION 10.2 • n=97 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=49 Participants
|
32 Participants
n=48 Participants
|
70 Participants
n=97 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=49 Participants
|
16 Participants
n=48 Participants
|
27 Participants
n=97 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=49 Participants
|
6 Participants
n=48 Participants
|
8 Participants
n=97 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
47 Participants
n=49 Participants
|
42 Participants
n=48 Participants
|
89 Participants
n=97 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=97 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
1 Participants
n=97 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=49 Participants
|
1 Participants
n=48 Participants
|
3 Participants
n=97 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=97 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=49 Participants
|
1 Participants
n=48 Participants
|
1 Participants
n=97 Participants
|
|
Race (NIH/OMB)
White
|
46 Participants
n=49 Participants
|
46 Participants
n=48 Participants
|
92 Participants
n=97 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=97 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
0 Participants
n=97 Participants
|
|
Region of Enrollment
United States
|
49 participants
n=49 Participants
|
48 participants
n=48 Participants
|
97 participants
n=97 Participants
|
|
PKD genotype
PKD1
|
37 Participants
n=49 Participants
|
28 Participants
n=48 Participants
|
65 Participants
n=97 Participants
|
|
PKD genotype
PKD2
|
7 Participants
n=49 Participants
|
10 Participants
n=48 Participants
|
17 Participants
n=97 Participants
|
|
PKD genotype
Other
|
1 Participants
n=49 Participants
|
4 Participants
n=48 Participants
|
5 Participants
n=97 Participants
|
|
PKD genotype
No mutation detected
|
2 Participants
n=49 Participants
|
4 Participants
n=48 Participants
|
6 Participants
n=97 Participants
|
|
PKD genotype
N/A
|
2 Participants
n=49 Participants
|
2 Participants
n=48 Participants
|
4 Participants
n=97 Participants
|
|
GFR
|
86.1 (ml/min/1.73 m²)
STANDARD_DEVIATION 20.6 • n=49 Participants
|
85.9 (ml/min/1.73 m²)
STANDARD_DEVIATION 19.0 • n=48 Participants
|
86.0 (ml/min/1.73 m²)
STANDARD_DEVIATION 19.7 • n=97 Participants
|
|
Vitamin B12
|
580.7 pg/mL
STANDARD_DEVIATION 350.8 • n=49 Participants
|
495.3 pg/mL
STANDARD_DEVIATION 202.3 • n=48 Participants
|
538.4 pg/mL
STANDARD_DEVIATION 288.8 • n=97 Participants
|
|
Glucose
|
88.6 mg/dL
STANDARD_DEVIATION 8.4 • n=49 Participants
|
90.9 mg/dL
STANDARD_DEVIATION 9.1 • n=48 Participants
|
89.7 mg/dL
STANDARD_DEVIATION 8.8 • n=97 Participants
|
|
HbA1c
|
5.2 % of total hemoglobin
STANDARD_DEVIATION 0.3 • n=48 Participants • Two participants are missing results.
|
5.2 % of total hemoglobin
STANDARD_DEVIATION 0.3 • n=47 Participants • Two participants are missing results.
|
5.2 % of total hemoglobin
STANDARD_DEVIATION 0.3 • n=95 Participants • Two participants are missing results.
|
|
Serum Creatinine
|
0.92 mg/dL
STANDARD_DEVIATION 0.24 • n=49 Participants
|
0.94 mg/dL
STANDARD_DEVIATION 0.23 • n=48 Participants
|
0.93 mg/dL
STANDARD_DEVIATION 0.23 • n=97 Participants
|
|
Systolic BP
|
122.2 mmHg
STANDARD_DEVIATION 13.1 • n=49 Participants
|
124.1 mmHg
STANDARD_DEVIATION 13.0 • n=48 Participants
|
123.1 mmHg
STANDARD_DEVIATION 13.0 • n=97 Participants
|
|
Diastolic BP
|
76.8 mmHg
STANDARD_DEVIATION 8.9 • n=49 Participants
|
74.6 mmHg
STANDARD_DEVIATION 8.5 • n=48 Participants
|
75.7 mmHg
STANDARD_DEVIATION 8.7 • n=97 Participants
|
|
Weight
|
78.5 kg
STANDARD_DEVIATION 16.9 • n=49 Participants
|
78.2 kg
STANDARD_DEVIATION 17.4 • n=48 Participants
|
78.4 kg
STANDARD_DEVIATION 17.0 • n=97 Participants
|
|
BMI
|
27.0 kg/m^2
STANDARD_DEVIATION 5.9 • n=49 Participants
|
26.6 kg/m^2
STANDARD_DEVIATION 4.5 • n=48 Participants
|
26.8 kg/m^2
STANDARD_DEVIATION 5.2 • n=97 Participants
|
|
Gastrointestinal Symptoms Rating Scale
|
1.4 scores on a scale
STANDARD_DEVIATION 0.5 • n=49 Participants
|
1.3 scores on a scale
STANDARD_DEVIATION 0.4 • n=48 Participants
|
1.4 scores on a scale
STANDARD_DEVIATION 0.4 • n=97 Participants
|
|
Short Form-36, Mental Component Summary
|
51.7 scores on a scale
STANDARD_DEVIATION 9.0 • n=49 Participants
|
53.1 scores on a scale
STANDARD_DEVIATION 7.9 • n=48 Participants
|
52.4 scores on a scale
STANDARD_DEVIATION 8.5 • n=97 Participants
|
|
Short Form-36, Physical Component Summary
|
52.2 scores on a scale
STANDARD_DEVIATION 6.5 • n=49 Participants
|
53.2 scores on a scale
STANDARD_DEVIATION 6.3 • n=48 Participants
|
52.7 scores on a scale
STANDARD_DEVIATION 6.4 • n=97 Participants
|
|
Mayo Imaging Class
Class 2
|
2 Participants
n=49 Participants
|
5 Participants
n=48 Participants
|
7 Participants
n=97 Participants
|
|
Mayo Imaging Class
Class 1A
|
9 Participants
n=49 Participants
|
6 Participants
n=48 Participants
|
15 Participants
n=97 Participants
|
|
Mayo Imaging Class
Class 1B
|
13 Participants
n=49 Participants
|
15 Participants
n=48 Participants
|
28 Participants
n=97 Participants
|
|
Mayo Imaging Class
Class 1C
|
14 Participants
n=49 Participants
|
12 Participants
n=48 Participants
|
26 Participants
n=97 Participants
|
|
Mayo Imaging Class
Class 1D
|
6 Participants
n=49 Participants
|
6 Participants
n=48 Participants
|
12 Participants
n=97 Participants
|
|
Mayo Imaging Class
Class 1E
|
4 Participants
n=49 Participants
|
4 Participants
n=48 Participants
|
8 Participants
n=97 Participants
|
|
Mayo Imaging Class
N/A
|
1 Participants
n=49 Participants
|
0 Participants
n=48 Participants
|
1 Participants
n=97 Participants
|
|
Height-adjusted total kidney volume
|
625.8 mL/m
STANDARD_DEVIATION 386.5 • n=48 Participants • One participant missing result.
|
750.9 mL/m
STANDARD_DEVIATION 547.8 • n=48 Participants • One participant missing result.
|
688.4 mL/m
STANDARD_DEVIATION 475.7 • n=96 Participants • One participant missing result.
|
|
Height-adjusted liver volume
|
1,224.1 mL/m
STANDARD_DEVIATION 490.7 • n=48 Participants • One participant missing result.
|
1,019.0 mL/m
STANDARD_DEVIATION 212.6 • n=48 Participants • One participant missing result.
|
1,121.6 mL/m
STANDARD_DEVIATION 390.0 • n=96 Participants • One participant missing result.
|
PRIMARY outcome
Timeframe: Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 monthsGSRS is a widely used, validated 15-item questionnaire used to assess GI symptom burden (minimum, maximum: 1, 7, where higher mean score is worse outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Change in the Gastrointestinal Symptoms Rating Scale (GSRS) to 24 Months
|
-0.04 score on a scale
Interval -0.18 to 0.1
|
-0.11 score on a scale
Interval -0.24 to 0.03
|
PRIMARY outcome
Timeframe: Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Tolerability was based on the first visit a participant responded no to the following question "Can you tolerate this dose of study drug the rest of your life?", which was asked at baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Drug Tolerability
|
21 Participants
|
14 Participants
|
PRIMARY outcome
Timeframe: 26 monthsPopulation: Participants who received and took metformin or placebo
Serious adverse events (SAE) occurring from the time a participant signs the informed consent (at the screening visit) until the end of the study, meeting 1 or more of the criteria of: 1) Resulting in death, 2) Non-elective hospitalization, 3) Life threatening (if patient continued on study drug would result in death), 4) Harming or disabling persistently or permanently , 5) Exceeding the nature, severity or frequency of risk described in the protocol or 6) Resulting in congenital anomaly.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Rate of Serious Adverse Events (SAE)
|
4 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Short Form-36 Quality of Life Physical Component Summary (SF-36 PCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Quality of Life Physical Component
|
-0.11 score on a scale
Interval -1.69 to 1.46
|
-0.51 score on a scale
Interval -2.05 to 1.03
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Short Form-36 Quality of Life Mental Component Summary (SF-36 MCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Quality of Life Mental Component
|
1.01 score on a scale
Interval -1.23 to 3.25
|
-0.11 score on a scale
Interval -2.29 to 2.08
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Odds ratio (OR) per month of back pain Often, Usually, or Always (vs. Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Back Pain Frequency Over the Past 3 Months Since Last Visit
|
0.95 odds ratio
Interval 0.9 to 1.0
|
0.92 odds ratio
Interval 0.88 to 0.98
|
SECONDARY outcome
Timeframe: Baseline, 2 weeks, and 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Estimated Glomerular Filtration Rate (eGFR)
|
-3.41 ml/min/1.73m^2
Interval -6.36 to -0.46
|
-6.14 ml/min/1.73m^2
Interval -9.04 to -3.24
|
SECONDARY outcome
Timeframe: Baseline, 6 months, 12 months, 18 months, 24 monthsPopulation: Intention to treat analysis
Annual percent change of height adjusted and natural log transformed total kidney volume \[ln(htTKV)\] was estimated with a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Total Kidney Volume From Magnetic Resonance Imaging
|
3.87 annual percent change
Interval 1.09 to 6.74
|
2.16 annual percent change
Interval -0.52 to 4.91
|
SECONDARY outcome
Timeframe: Baseline, 6 months, 12 months, 18 months, 24 monthsPopulation: Intention to treat analysis
Annual percent change of height adjusted and natural log transformed total kidney cyst volume \[ln(htTKCV)\] was estimated with a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Total Kidney Cyst Volume From Magnetic Resonance Imaging
|
9.37 annual percent change
Interval 3.82 to 15.22
|
5.36 annual percent change
Interval 0.13 to 10.86
|
SECONDARY outcome
Timeframe: Baseline, 6 months, 12 months, 18 months, 24 monthsPopulation: Intention to treat analysis
Annual percent change of height adjusted and natural log transformed liver volume \[ln(htLV)\] was estimated with a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Liver Volume From Magnetic Resonance Imaging
|
1.60 annual percent change
Interval 0.02 to 3.21
|
1.21 annual percent change
Interval -0.32 to 2.77
|
SECONDARY outcome
Timeframe: Baseline, 6 months, 12 months, 18 months, 24 monthsPopulation: Intention to treat analysis
Annual percent change of height adjusted and natural log transformed liver cyst volume \[ln(htLCV)\] was estimated with a linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Liver Cyst Volume From Magnetic Resonance Imaging
|
12.72 annual percent change
Interval 3.47 to 22.79
|
10.94 annual percent change
Interval 1.73 to 20.99
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Odds ratio (OR) per month of abdominal fullness interfered Often, Usually, or Always (vs. Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Frequency Abdominal Fullness Interfered With Ability to Perform Usual Physical Activity Over the Past 3 Months Since Last Visit.
|
1.00 odds ratio
Interval 0.89 to 1.13
|
0.99 odds ratio
Interval 0.87 to 1.12
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Odds ratio (OR) per month of pain interfered with sleep Quite a bit or Extremely (vs. Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Interference of Pain With Sleep Over the Past 3 Months Since Last Visit
|
1.00 odds ratio
Interval 0.87 to 1.14
|
0.97 odds ratio
Interval 0.88 to 1.07
|
SECONDARY outcome
Timeframe: Baseline, 1 month, 3 months and every 3 months thereafter to 24 monthsPopulation: Intention to treat analysis
Odds ratio (OR) per month of pain interfered with strenuous physical activity Quite a bit or Extremely (vs. Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Outcome measures
| Measure |
Metformin
n=49 Participants
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 Participants
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Interference of Pain With Strenuous Physical Activity Over the Past 3 Months Since Last Visit
|
0.99 odds ratio
Interval 0.93 to 1.06
|
0.95 odds ratio
Interval 0.9 to 1.01
|
Adverse Events
Metformin
Serious events: 4 serious events
Other events: 21 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Metformin
n=49 participants at risk
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 participants at risk
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Infections and infestations
Other - diarrhea (c. difficile infection)
|
2.0%
1/49 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Musculoskeletal and connective tissue disorders
Other - bone fracture
|
2.0%
1/49 • Number of events 2 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Nervous system disorders
Seizure
|
2.0%
1/49 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Nervous system disorders
Other - lightheadedness
|
0.00%
0/49 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
2.1%
1/48 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
2.0%
1/49 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Psychiatric disorders
Suicide attempt
|
2.0%
1/49 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Surgical and medical procedures
Other - umbilical hernia
|
2.0%
1/49 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Infections and infestations
Appendicitis perforated
|
0.00%
0/49 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
2.1%
1/48 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Infections and infestations
Other - urinary tract infection and renal cyst hemorrhage (mild)
|
0.00%
0/49 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
2.1%
1/48 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Renal and urinary disorders
Other - renal cyst
|
0.00%
0/49 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
2.1%
1/48 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Renal and urinary disorders
Other - renal cyst rupture
|
0.00%
0/49 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
2.1%
1/48 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Vascular disorders
Hematoma
|
2.0%
1/49 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
Other adverse events
| Measure |
Metformin
n=49 participants at risk
Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms.
|
Placebo
n=48 participants at risk
Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
42.9%
21/49 • Number of events 42 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
27.1%
13/48 • Number of events 18 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Nausea
|
34.7%
17/49 • Number of events 29 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
20.8%
10/48 • Number of events 15 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Abdominal Pain
|
16.3%
8/49 • Number of events 11 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
18.8%
9/48 • Number of events 9 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Flatulence
|
20.4%
10/49 • Number of events 12 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
14.6%
7/48 • Number of events 7 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Constipation
|
12.2%
6/49 • Number of events 6 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
14.6%
7/48 • Number of events 7 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Abdominal Distension
|
14.3%
7/49 • Number of events 8 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
8.3%
4/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Vomiting
|
10.2%
5/49 • Number of events 6 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
12.5%
6/48 • Number of events 6 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Dyspepsia
|
6.1%
3/49 • Number of events 5 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
4.2%
2/48 • Number of events 2 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Bloating
|
10.2%
5/49 • Number of events 5 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
2.1%
1/48 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Other - Loss Of Appetite
|
4.1%
2/49 • Number of events 2 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
6.2%
3/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Gastrointestinal disorders
Other - Loose Stools
|
6.1%
3/49 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.2%
5/49 • Number of events 5 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
18.8%
9/48 • Number of events 11 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
10.2%
5/49 • Number of events 6 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
14.6%
7/48 • Number of events 8 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Other - Upper Respiratory Infection
|
6.1%
3/49 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
8.3%
4/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
4.1%
2/49 • Number of events 2 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
8.3%
4/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Renal and urinary disorders
Hematuria
|
6.1%
3/49 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
8.3%
4/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Renal and urinary disorders
Other - Uti
|
4.1%
2/49 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
6.2%
3/48 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Renal and urinary disorders
Other - Kidney Pain
|
2.0%
1/49 • Number of events 1 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
6.2%
3/48 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Nervous system disorders
Headache
|
16.3%
8/49 • Number of events 11 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
12.5%
6/48 • Number of events 8 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Nervous system disorders
Dizziness
|
8.2%
4/49 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
6.2%
3/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
General disorders
Fatigue
|
8.2%
4/49 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
10.4%
5/48 • Number of events 5 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
General disorders
Chills
|
0.00%
0/49 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
6.2%
3/48 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
8.2%
4/49 • Number of events 5 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
8.3%
4/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Metabolism and nutrition disorders
Dehydration
|
6.1%
3/49 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
0.00%
0/48 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Infections and infestations
Urinary Tract Infection
|
8.2%
4/49 • Number of events 6 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
6.2%
3/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Psychiatric disorders
Anxiety
|
6.1%
3/49 • Number of events 3 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
4.2%
2/48 • Number of events 2 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
|
Psychiatric disorders
Depression
|
0.00%
0/49 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
8.3%
4/48 • Number of events 4 • Adverse event were data collected at 2, 4, and 6 weeks during the titration period and every 3 months thereafter through 26 months.
Adverse events and deaths were not collected by dose level.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place