Trial Outcomes & Findings for Trial of an Intervention to Improve Metformin Persistence and Adherence (NCT NCT03467763)

Last Updated: 2020-12-07

Results Overview

The primary outcome of this portion of the study will be the global satisfaction subscale of the Treatment Satisfaction Questionnaire for Medication (TSMQ II). The TSQM II is a 12-question survey with four satisfaction domains: effectiveness, side effects, convenience and global satisfaction. Each domain is described by a single numeric score. For each of these domains the lowest possible score (less satisfaction, ie a worse outcome) is 0, the highest (more satisfaction, ie a better outcome) is 100. We report this score global satisfaction domain (ie, subscale). (Note that the global satisfaction score is not a synthesis of the various subscales associated with each domain. It is a subscale in its own right comprised of distinct questions.)

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

13 participants

Primary outcome timeframe

4-months

Results posted on

2020-12-07

Participant Flow

Please note that results have been presented in a single study arm as the order in which participants received drug or placebo was unique for many patients, so that reporting a separate arm for each sequence of drug and placebo exposure would have resulted in reporting individual level results, potentially compromising patient confidentiality.

Participant milestones

Participant milestones
Measure	Metformin Hydrochloride Extended Release and Placebo Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. Patients were assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Individual encapsulations of metformin will contain dosages of 250 mg or 500 mg. Patients were assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of placebo, followed by 500 mg placebo, 750 mg, and 1,000 mg placebo with each treatment period separated by a 2-week course of metformin XR in the same increments of dosage. Placebo oral capsule: Placebo capsule
Overall Study STARTED	13
Overall Study Weeks 1-2	13
Overall Study Weeks 3-4	10
Overall Study Weeks 5-6	8
Overall Study Weeks 7-8	7
Overall Study Weeks 9 - 10	6
Overall Study Week 11-12	6
Overall Study Weeks 13-14	2
Overall Study Weeks 15-16	2
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Metformin Hydrochloride Extended Release and Placebo Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. Patients were assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Individual encapsulations of metformin will contain dosages of 250 mg or 500 mg. Patients were assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of placebo, followed by 500 mg placebo, 750 mg, and 1,000 mg placebo with each treatment period separated by a 2-week course of metformin XR in the same increments of dosage. Placebo oral capsule: Placebo capsule
Overall Study Lost to Follow-up	1
Overall Study Protocol Violation	2

Baseline Characteristics

Trial of an Intervention to Improve Metformin Persistence and Adherence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin Hydrochloride Extended Release and Placebo n=13 Participants Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. Patients were assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Individual encapsulations of metformin will contain dosages of 250 mg or 500 mg. Patients were assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of placebo, followed by 500 mg placebo, 750 mg, and 1,000 mg placebo with each treatment period separated by a 2-week course of metformin XR in the same increments of dosage. Placebo oral capsule: Placebo capsule
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=99 Participants
Age, Categorical >=65 years	3 Participants n=99 Participants
Sex: Female, Male Female	13 Participants n=99 Participants
Sex: Female, Male Male	0 Participants n=99 Participants
Race/Ethnicity, Customized Asian	1 Participants n=99 Participants
Race/Ethnicity, Customized Black	2 Participants n=99 Participants
Race/Ethnicity, Customized White	6 Participants n=99 Participants
Race/Ethnicity, Customized Unknown or Not Reported	3 Participants n=99 Participants
Race/Ethnicity, Customized More Than One Race	1 Participants n=99 Participants
Region of Enrollment United States	13 participants n=99 Participants

PRIMARY outcome

Timeframe: 4-months

Population: The results from 3 participants were not analyzed as these participants were lost to follow-up or violated study protocol. Results are presented in two study arms, as reporting a separate arm for each sequence of drug and placebo exposure would have resulted in reporting individual level results, potentially compromising patient confidentiality. All patients contributed data to both arms except for 2 patients who had missing data during their placebo-exposed time.

Outcome measures

Outcome measures
Measure	Metformin Hydrochloride Extended Release n=10 Participants Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. The resulting regimen was 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. This arm includes only the person-time exposed to metformin XR.	Placebo n=8 Participants Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. The resulting regimen was 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. This arm includes only the person-time exposed to placebo.
Treatment Satisfaction as Measured by the Treatment Satisfaction Questionnaire for Medication (TSQM II)	39.42 score on a scale Standard Error 5.09	51.92 score on a scale Standard Error 4.57

PRIMARY outcome

Timeframe: 6-months

Population: Results from 3 participants not analyzed as these participants were lost to follow-up or violated study protocol. Results are presented in a single study arm, as reporting a separate arm for each sequence of drug and placebo exposure would have resulted in reporting individual level results, and because this outcome occurs only once per patient after the end of all placebo and metformin exposure periods it could not reported as two arms (placebo versus metformin.)

For aim 2 of this study, the primary objective is to test the hypothesis \> 30% of the patients enrolled in this study are able to tolerate (continue taking) a higher-dose of metformin at 6 months than they were taking at baseline.

Outcome measures

Outcome measures
Measure	Metformin Hydrochloride Extended Release n=10 Participants Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. The resulting regimen was 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. This arm includes only the person-time exposed to metformin XR.	Placebo Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. The resulting regimen was 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. This arm includes only the person-time exposed to placebo.
Number of Subjects Able to Tolerate Higher Dose of Metformin,	2 Participants	—

SECONDARY outcome

Timeframe: Reoccurring every 2-weeks for 4-months

For aim 1, the secondary objectives are to test the hypotheses that scores on a gastrointestinal symptom questionnaire are the same between between placebo and intervention periods; that adherence is the same between periods; and that the answer to the question 'Were you taking placebo or metformin for the past two weeks' is correct no more often than would be predicted by chance. Each question in the Gastrointestinal Symptom Rating Scale (GSRS) is scored on scale from 1 to 7 with 1 being no discomfort at all and 7 being very severe discomfort. The GSRS has separate questions to separately assess each of a range of potential GI symptoms (abdominal pain, reflux, diarrhoea, indigestion and constipation). Each symptom area can be described with the mean score of its contributing questions (so that the range in each symptom area is also 1 to 7, with lower numbers being better)

Outcome measures

Outcome measures
Measure	Metformin Hydrochloride Extended Release n=10 Participants Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. The resulting regimen was 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. This arm includes only the person-time exposed to metformin XR.	Placebo n=10 Participants Metformin Extended Release Oral Tablet: Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Participants took their baseline medication plus escalating doses of metformin in 250 mg increments, alternating with placebo in a randomized, double-blinded fashion. The resulting regimen was 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. This arm includes only the person-time exposed to placebo.
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) Abdominal Pain	2.308 units on a scale Standard Error 0.21	2.346 units on a scale Standard Error 0.17
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) Reflux	1.885 units on a scale Standard Error 0.24	1.78 units on a scale Standard Error 0.23
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) Diarrhea	2.564 units on a scale Standard Error 0.29	2.346 units on a scale Standard Error 0.26
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) Constipation	2.705 units on a scale Standard Error 0.23	2.667 units on a scale Standard Error 0.28
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) Indigestion	2.50 units on a scale Standard Error 0.19	2.296 units on a scale Standard Error 0.26

Adverse Events

Metformin Hydrochloride Extended Release and Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. James Flory

Memorial Sloan Kettering Cancer Center

Phone: 6468883790

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place