An Open Study to Evaluate Whether Pack Size Affects Compliance of Metformin Treatment in Subjects With Type II Diabetes

Study Overview
=================
Brief Summary
-----------------
MTF116086 is an open-label, randomised, parallel-design study in subjects with type II diabetes. The study is site-based, with local pharmacies serving as the sites and pharmacists as principal investigators for the sites. All subjects will enter an initial 8-week observational phase during which purchase behaviour and compliance with usual metformin use will be observed and recorded. At the end of the observational phase, subjects will be randomised to one of the two arms (metformin small pack vs. metformin large pack) for a 20-week interventional phase. The medication in the interventional phase is provided to the subjects free of charge. HbA1c will be collected for all subjects during Week 0, Week 8, and Week 28. Subjects will be asked questions about their tablet compliance, their satisfaction with the pack size they received and reasons for missing doses throughout the interventional phase by the pharmacist. The pharmacy visit on Week 28 will be end of the study.

Official Title
-----------------
A Pharmacy Based Open Study to Evaluate Whether Pack Size Affects Compliance for Subjects Diagnosed With Diabetes Type II Who Are Established on Metformin Treatment

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Metformin Small Pack
* Drug: Metformin Large Pack


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females of age >=18 years Diagnosis of type II diabetes HbA1c value no higher than 9.0% Evidence of physician-supplied prescription for metformin use Stable dose of metformin for 3 months prior to enrolment Written informed consent from the subject Exclusion Criteria: Current use of any anti-diabetic medication other than metformin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin Small Pack Arm<br>All subjects in the study will be initially followed for an 8-week observational phase during which subjects will visit the pharmacy and purchase metformin following their usual routines. After 8-weeks subjects will be randomised to one of the 2 treatments arms. Subjects in the metformin small pack arm will receive medication free of charge in a small pack. Dosing of metformin will not be dictated by the protocol. Subjects will remain on their prescribed dose of metformin throughout the study, unless a change is recommended by their physician. | Drug: Metformin Small Pack<br>* A single small pack of metformin will consist of a blister package containing 10 pills with a patient information leaflet in local language. The small packs will be available at each site in the following doses: 500 mg, 850 mg, and 1000 mg. The small pack size of metformin is not yet marketed. Small pack metformin will be provided by GSK as GSK brand metformin.<br>|
| Experimental: Metformin Large Pack Arm<br>All subjects in the study will be initially followed for an 8-week observational phase during which subjects will visit the pharmacy and purchase metformin following their usual routines. After 8-weeks subjects will be randomised to one of the 2 treatments arms. Subjects in the metformin large pack arm will receive medication free of charge in a large, monthly pack. Dosing of metformin will not be dictated by the protocol. Subjects will remain on their prescribed dose of metformin throughout the study, unless a change is recommended by their physician. | Drug: Metformin Large Pack<br>* The large pack will consist of 1 month's supply of metformin.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c Values at Week 28 | HbA1c was tested with a point-of-care device, which required a finger prick to obtain blood and provided an immediate result upon analysis in the device. HbA1c was tested at pharmacy visits corresponding to three time points: enrollment (Week 0), Baseline (Week 8), and End of Study (Week 28). The difference in the mean change from Baseline was to be calculated between the treatment arms (small pack minus large pack), and the 2-sided 95% confidence interval for the difference in mean change in HbA1c was to be calculated. However, because the study was terminated early, and the sample size was reduced, the statistical hypotheses defined in the protocol were not tested due to insufficient power. Therefore, the final analyses were limited to descriptive statistics. The percentage HbA1c is a measure of how much of the hemoglobin in the blood has become glycated (chemically bounded to glucose). | Baseline (Week 8) and Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Compliance Throughout the Interventional Phase | Compliance for the study was estimated as a percentage, with the denominator defined as the number of pills dispensed by the pharmacist and the numerator defined as the number of pills taken, accounting for remaining pills at subsequent pharmacy visits. | From Randomization to Week 28 | 
| Mean Percent Compliance Throughout the Observational Phase, Per Treatment They Were Randomized to in the Interventional Phase | Compliance was estimated during the 8-week Observational Phase for usual metformin treatment. During the Observational Phase, compliance was measured by monitoring the number of pill dispensed and the return of the pills or tablets. | From enrollment to Week 8 | 
| Number of Participants Who Took Zero Metformin Pills for the Indicated Number of Days | The number of days on which no metformin pills were taken by participants was summarized. | Week 28 | 
| Number of Participants With Diabetes Disease Management Modifications | Throughout the duration of the study, participants remained on their recommended metformin dosing regimens, unless a change in metformin dose was prescribed by their physician. The number of participants who received additional diabetes therapy for the management of diabetes was summarized. | Week 28 | 
| Number of Participants Who Required a Non-routine Health Care Professional Visit for Diabetes | The number of participants who visited a health care professional for diabetes management during the study was summarized. | Week 28 | 
| Number of Participants Who Preferred Their Treatment Regimens (Interventional Arm Treatment [Large or Small Pack Metformin]) to How They Previously Took Their Medication | Number of participants who preferred their treatment regimens (interventional arm treatment [large or small pack metformin]) to how they previously took their medication are presented. | Week 28 | 
| Number of Participants Who Missed Metformin Days/Doses for the Indicated Reasons | The number of particiapnts who missed days or doses of metformin was summarized. | Week 28 | 
| Number of Participants Withdrawn From the Study Due to the Following Reasons: Withdrawal of Informed Consent; Lost to Follow-up | The number of participants who voluntarily discontinued participation in the study at any time or who were withdrawn by the investigator for pre-defined reasons was summarized. | Week 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Socioeconomic category, Medication compliance, Metformin, small pack