Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen for T2DM During Ramadan

NCT02694263 | Completed Phase 4 DMC

• 1 other identifier: 0527
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to determine if the addition of Canagliflozin (Invokana™) therapy to monotherapy of metformin is more effective at achieving the double composite endpoint of a reduction in HbA1c (≥ 0.3%) and weight loss (≥1kg) 3-4 weeks post-Ramadan. The study will also include patients currently on dual therapy, specifically metformin plus a sulphonylurea, pioglitazone or repaglinide to determine whether switching to metformin plus Canagliflozin (Invokana™) is more effective at achieving the composite endpoint compared to those remaining on previous dual therapy. There are a number of secondary outcomes including weight loss, rates of hypoglycaemia, blood pressure and a number of biochemical endpoints.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• HbA1c + weight loss

  Double composite endpoint of a change in HbA1c (≥ 0.3%) and weight loss (≥1kg) between baseline and 3-4 weeks post-Ramadan.

  Baseline and 3-4 weeks post-Ramadan

Secondary Outcomes (31)

• HbA1c + weight loss + Hypoglycaemic events

  Baseline and 3-4 weeks post-Ramadan

• HbA1c

  Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.

• Fructosamine

  Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.

• Body weight (kg)

  Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.

• Systolic blood pressure (mm Hg)

  Baseline and (a) 3-4 weeks post-Ramadan, (b) 12 weeks post-Ramadan and (c) 12 months post-Ramadan.

Study Arms (5)

Canagliflozin + Metformin

EXPERIMENTAL

Canagliflozin + metformin (using the participant's current dose, or dose recommended by the study clinician). An initial dose of 100mg once daily of Canagliflozin will be prescribed, and this will be titrated up to a maximum of 300mg once daily.

Drug: Canagliflozin

Repaglinide + Metformin

ACTIVE COMPARATOR

Repaglinide + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). An initial dose of 0.5mg once daily where no prior treatment has been given will be prescribed. However, where prior treatment has been in place, an initial dose of 1-2mg once daily will be started and this will be titrated up to a maximum dose of 4mg daily.

Drug: Repaglinide

Pioglitazone + Metformin

ACTIVE COMPARATOR

Piogliazone + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). For example, Pioglitazone dose will initially be 15mg or 30mg once daily. If the response is inadequate, the maximum daily dosage will be increased to 45mg once daily.

Drug: Pioglitazone

Gliclazide + Metformin

ACTIVE COMPARATOR

Gliclazide + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). For example, Gliclazide dose will initially be 40-80 mg once daily, up to maximum dose of 160mg twice daily..

Drug: Gliclazide

Glimepiride + Metformin

ACTIVE COMPARATOR

Glimepiride + Metformin (using the participant's current dose(s), or dose recommended by the study clinician). Glimepiride will initially be administered as 1mg once daily, up to a maximum dose of 4mg once daily.

Drug: Glimepiride

Interventions

Canagliflozin DRUG

Comparison of Canagliflozin (Invokana™) vs. standard dual therapy (Repaglinide, Pioglitazone, Gliclazide or Glimepiride) for the treatment of Type 2 Diabetes.

Also known as: Invokana

Canagliflozin + Metformin

Repaglinide DRUG

Comparison of Canagliflozin (Invokana™) vs. standard dual therapy (Repaglinide) for the treatment of Type 2 Diabetes.

Also known as: Prandin

Repaglinide + Metformin

Pioglitazone DRUG

Comparison of Canagliflozin (Invokana™) vs. standard dual therapy (Pioglitazone) for the treatment of Type 2 Diabetes.

Also known as: Actos

Pioglitazone + Metformin

Gliclazide DRUG

Comparison of Canagliflozin (Invokana™) vs. standard dual therapy (Gliclazide) for the treatment of Type 2 Diabetes.

Also known as: Diamicron

Gliclazide + Metformin

Glimepiride DRUG

Comparison of Canagliflozin (Invokana™) vs. standard dual therapy (Glimepiride) for the treatment of Type 2 Diabetes.

Also known as: Amaryl

Glimepiride + Metformin

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able, in the opinion of the Investigator, and willing to give informed consent
• Age ≥ 25 years old
• Established T2DM (≥ 3 months) on stable dose monotherapy (metformin only for ≥ 8 weeks prior to enrolment) OR stable dose dual therapy (metformin plus either repaglinide, a sulphonylurea or pioglitazone or DPP-4 inhibitor for ≥ 8 weeks prior to enrolment)
• HbA1c between 6.6 - 11% (49mmol/mol - 97mmol/mol) at the screening visit
• Individuals intending to fast during the holy month of Ramadan

You may not qualify if:

• Unable, in the opinion of the Investigator, and unwilling to provide informed consent
• Aged \< 25 years old
• Established T2DM (≤ 3 months) on medication for fewer than 8 weeks prior to enrolment
• HbA1c ≤6.5 and ≥11.1%
• Individuals not intending to fast during the holy month of Ramadan
• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. The latter includes avoiding sex, hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization, consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study, or not heterosexually active. Furthermore, subjects who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study. Women of childbearing potential must have a negative urine pregnancy test at baseline.
• Suffer from terminal illness
• Have renal disease that requires immunosuppressive therapy, dialysis or transplant
• Have nephrotic syndrome or inflammatory renal disease
• Have an estimated glomerular filtration rate (eGFR) \<60ml/min/1.73m2 at screening
• Have serum creatinine levels \>132.6μmol/L for men or \>123.8μmol/L for women
• Impaired liver function (ALAT ≥ 2.5 times upper limit of normal)
• Known Hepatitis B antigen or Hepatitis C antibody positive
• Clinically significant active cardiovascular disease (including history of myocardial infarction, unstable angina, previous revascularization procedure or cerebrovascular accident) within the past 6 months before screening
• Have uncontrolled hypertension (defined as systolic blood pressure ≥180mm/Hg and diastolic ≥100mm/Hg in the supine position after \>5minutes rest with confirmed compliance to antihypertensive medication)

Sponsors & Collaborators

• University of Leicester: lead
• University Hospital Birmingham: collaborator

Study Sites (2)

University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, LE5 4PW, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

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MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Canagliflozin; repaglinide; Pioglitazone; Gliclazide; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Thiazolidinediones; Thiazoles; Azoles; Benzenesulfonamides; Sulfonamides; Amides; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones

Study Officials

• Melanie J Davies, MBBS MD FRCP FRCGP

  University of Leicester

  PRINCIPAL INVESTIGATOR

• Wasim Hanif, MBBS MD FRCP

  University Hospital Birmingham NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2016
• First Posted: February 29, 2016
• Study Start: July 1, 2016
• Primary Completion: September 13, 2018
• Study Completion: September 13, 2018
• Last Updated: January 30, 2020

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)