Trial Outcomes & Findings for Pharmacogenetics of Metformin Action in PCOS (NCT NCT00703508)

Results Overview

Responders were defined as those that had a doubling of baseline ovulation rate estimated by self-report of menstrual history.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

55 participants

Primary outcome timeframe

9 months

Results posted on

2017-06-14

Participant Flow

55 subjects were enrolled, however some subjects failed to meet eligibility criteria resulting in 26 subjects initiating and completing all study phases.

Participant milestones

Participant milestones
Measure	Metformin Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration Metformin 500 mg tablet: Metformin 500 mg tablets; two tablets every 12 hours for 9 months
Overall Study STARTED	26
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacogenetics of Metformin Action in PCOS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin n=26 Participants Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration Metformin 500 mg tablet: Metformin 500 mg tablets; two tablets every 12 hours for 9 months
Age, Continuous	27.9 years STANDARD_DEVIATION 4.2 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
BMI	35.0 kg/m^2 STANDARD_DEVIATION 7.6 • n=5 Participants

PRIMARY outcome

Timeframe: 9 months

Responders were defined as those that had a doubling of baseline ovulation rate estimated by self-report of menstrual history.

Outcome measures

Outcome measures
Measure	G/G Genotype n=26 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours	C/G Genotype n=26 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours	C/C Genotype n=26 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Number of Responders/Non-responders for Each STK11 rs8111699 Genotype (C/G, C/C, G/G) non-responders	3 participants	4 participants	1 participants
Number of Responders/Non-responders for Each STK11 rs8111699 Genotype (C/G, C/C, G/G) responders	6 participants	7 participants	5 participants

PRIMARY outcome

Timeframe: 9 months

Ovulations were determined by measurement of daily urine pregnanediol-3-glucuronide or weekly progesterone levels over 6-9 months of study duration for each participant. The ovulation rate was calculated as the number of confirmed ovulation events per months of study participation.

Outcome measures

Outcome measures
Measure	G/G Genotype n=9 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours	C/G Genotype n=11 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours	C/C Genotype n=6 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Ovulation Rate Over Study Duration for STK11 Genotypes CC, CG and GG	0.47 ovulations/month Standard Deviation 0.310	0.36 ovulations/month Standard Deviation 0.396	0.34 ovulations/month Standard Deviation 0.336

SECONDARY outcome

Timeframe: 9 months

Population: Individuals that were lost to follow up had missing data on testosterone and OGTT (oral glucose tolerance testing) for Matsuda index.

Bivariate fit (RSquare with P values) of ovulation rate post treatment by change in total testosterone and Matsuda Index for each of the 3 genotypes (G/G, C/G, C/C)

Outcome measures

Outcome measures
Measure	G/G Genotype n=9 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours	C/G Genotype n=7 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours	C/C Genotype n=3 Participants Metformin tablet, 500 mg per tablet, 2 tablets every 12 hours
Determine in Which Genotype(s) Frequency of Ovulation Correlates With Improvement in Reduction in Total Testosterone and Insulin Sensitivity as Measured by the Matsuda Index. Ovulation rate vs Testosterone post treatment	0.138956 Correlation coefficient (r^2)	0.035449 Correlation coefficient (r^2)	0.049263 Correlation coefficient (r^2)
Determine in Which Genotype(s) Frequency of Ovulation Correlates With Improvement in Reduction in Total Testosterone and Insulin Sensitivity as Measured by the Matsuda Index. Ovulation rate vs Matsuda Index post treatment	0.27144 Correlation coefficient (r^2)	0.01918 Correlation coefficient (r^2)	0.132059 Correlation coefficient (r^2)

Adverse Events

Metformin

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Metformin n=26 participants at risk Metformin tablet, 500 mg/tablet, 2 tablets every twelve hours, 9 months duration Metformin 500 mg tablet: Metformin 500 mg tablets; two tablets every 12 hours for 9 months
Blood and lymphatic system disorders Anemia	3.8% 1/26 • Number of events 1 • For entire 9 months of study plus 30 days after study completion

Additional Information

Dr. Kai Cheang

Virginia Commonwealth University

Phone: (804) 828-2257

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place