Polypill Versus Metformin in New Onset Type 2 Diabetes (PiVOT)

Polypill Versus Metformin in New Onset Type 2 Diabetes: a Low Dose Triple Therapy Polypill Versus Metformin for Glycaemic Control in Newly Diagnosed Type 2 Diabetes

The goal of this clinical trial is to learn about the effect of the GMRx-4 IR polypill compared to metformin monotherapy on glycosylated haemoglobin (HbA1c) when used as first line therapy in adults with recently diagnosed Type 2 Diabetes. The main question it aims to answer is:

That the GMRx-4 IR polypill, compared to metformin, will improve glucose lowering in those with recently diagnosed Type 2 Diabetes.

Participants will be required to take either:

One capsule of the GMRx-4 IR polypill each morning and one 175mg metformin capsule each evening for 16 weeks.

Or One metformin 500mg capsule each morning and each evening for 16 weeks.

Participants will not know which of the two treatment regimens they will be taking. Participants will be provided with the necessary guidance information, equipment, online support and telephone/video calls from trained members of the study team to complete the study procedures at home although some support from a Healthcare Professional either at home or at a clinic will be offered if needed. The study will involve participants completing the following information and procedures and reporting electronically:

Medical History (conditions and treatments) Gender Age Ethnicity/Race Weight Height Blood Pressure Heart Rate Blood collection for measurement of HbA1c (average blood glucose levels over a period of time), fasting glucose, creatinine and estimated glomerular filtration rate (eGFR) for kidney function, cholesterol, pregnancy (if not measured in a urine sample) Urine pregnancy test in women of child-bearing potential Concomitant Medications taken Safety outcomes Tolerability to the study treatment Adherence with taking the study treatment The number of any unused study treatment capsules

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Metformin; Drug: Metformin; Drug: GMRx-4 IR polypill - sitagliptin, dapagliflozin, metformin

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kevin Spivey; Phone Number: +44 7587 328361; Email: kspivey@george-medicines.com
• Study Contact Backup: Name: Rene Gonzalez; Phone Number: +44 7392 399404; Email: rgonzalez@george-medicines.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥18 years;
2. Diagnosis of Type 2 Diabetes (T2D) within 24 months;
3. Drug naïve or using metformin monotherapy at ≤1g daily;
4. Body mass index between 18.5 and 45 kg/m2;
5. HbA1c ≥6.0% (metformin monotherapy) or ≥6.5% (drug naïve), and ≤12%;
6. eGFR ≥45 ml/min/1.73m2;
7. Signed informed consent; and
8. Willingness to take a pregnancy test prior to starting treatment (participants of childbearing potential).

Exclusion Criteria:

1. There is a definite contraindication to either metformin, SGLT2 inhibitors or Dipeptidyl-peptidase 4 (DPP4) inhibitors;
2. There is a definite indication for an SGLT2 inhibitor;
3. A known situation where medication might be altered for a significant length of time (e.g., planned surgery);
4. Moderate or severe anaemia (Hb< 100g/L women and <110g/L in men), haemolytic anaemia or known haemoglobinopathy (which may affect the accurate measurement of HbA1c);
5. Unlikely to complete the trial, adhere to the trial or complete study contacts, including at-home pathology tests, according to investigator judgement; or
6. Known or suspected pregnancy or breast-feeding;
7. Participants of childbearing potential (participants who are anatomically and physiologically capable of becoming pregnant), or have a partner of childbearing potential, not willing to use highly effective contraceptive for the 16-week duration of the trial, and who do not confirm a negative pregnancy test before starting the drug;
8. Any severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgement of the Investigator, and in discussion with the Medical Monitor, would make the participant inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin IR 500mg in the morning and at night; One metformin IR 500mg capsule in the morning and at night. Capsules are taken with, or just after, food, and swallowed whole with water. Capsules will be taken at, or as close as possible to, the same time of morning and the same time of evening each day for 16 weeks.	Drug: Metformin; As described previously - Experimental Arm, 175mg at night; Drug: Metformin; As described previously - Active Comparator Arm, 500mg in the morning and 500mg at night
Experimental: GMRx-4 IR polypill in the morning and metformin Immediate Release (IR)175mg at night; One GMRx-4 IR polypill capsule (metformin IR 175mg + dapagliflozin 2.5mg + sitagliptin 17.5mg) in the morning and one metformin IR 175mg capsule at night. Capsules are taken with, or just after, food, and swallowed whole with water. Capsules will be taken at, or as close as possible to, the same time of morning (GMRx-4 IR) and the same time of evening (metformin 175mg) each day for 16 weeks.	Drug: Metformin; As described previously - Experimental Arm, 175mg at night; Drug: Metformin; As described previously - Active Comparator Arm, 500mg in the morning and 500mg at night; Drug: GMRx-4 IR polypill - sitagliptin, dapagliflozin, metformin; As described previously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glycosylated haemoglobin (HbA1c)	Change in glycosylated haemoglobin (HbA1c) from baseline to 16 weeks	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasting plasma glucose	Change in fasting plasma glucose from baseline to 16 weeks	16 weeks
Change in cholesterol	Change in fasting total cholesterol, LDL-cholesterol and HDL-cholesterol from baseline to 16 weeks	16 weeks
Change in triglycerides	Change in fasting triglycerides from baseline to 16 weeks	16 weeks
Change in blood pressure	Change in systolic and diastolic blood pressure from baseline to 16 weeks	16 weeks
Change in weight in kilograms	Change in weight from baseline to 16 weeks	16 weeks
Medication adherence	Medication adherence throughout the trial. Adherence will be assessed by self-report surveys entered directly into the ePRO platform (eCRF).	16 weeks
Medication tolerability	Medication tolerability throughout the trial (based on permanent drug cessation due to side effects and incidence of reported side effects). Tolerability will be assessed by recording of adverse effects into self-report surveys, and adverse events identified by the Investigator during study contacts, entered directly into the ePRO platform (eCRF).	16 weeks

Collaborators and Investigators

• Sponsor: George Medicines PTY Limited
• Collaborators: The George Institute; Brandon Biocatalyst

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: March 31, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): April 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: GMRx-4 IR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: If the sponsor receives a request for study-level data listing, then such requests will be reviewed by a committee that is composed of sponsor representation and steering committee members.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No