Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients

Conditions

• Diabetes Mellitus, Type 2

Eligibility Criteria

Sex

ALL

Age

18 Years - 74 Years

Healthy Volunteers

Not accepted

Interventions

• Canakinumab — DRUG
  Canakinumab lyophilized cake (25 mg and 150 mg in individual 6 mL glass vials ) was reconstituted and then used to dilute the 25mg or 150mg solutions to make 5mg, 15mg and 50mg injections.
• Metformin — DRUG
  Before randomization, in drug naïve patients at a dose of 1000 mg with the evening meal or 500 mg b.i.d. (twice daily) with two main meals. At the randomization visit, patients were prescribed with no less than 1,000mg/day.
• Placebo — DRUG
  Placebo lyophilized cake will be reconstituted and then used to dilute the 25mg or 150mg solutions to make 5mg, 15mg and 50mg injections.

Study Details

This was a four month dose ranging study followed by a 24 to 48 month extension at the selected dose to characterize the safety and efficacy of the injectable IL-1B (interleukin 1, beta) antagonist canakinumab in the treatment of patients with Type 2 diabetes mellitus (T2DM) already treated on maximum dose metformin.

Key Dates

Start date

Apr 30, 2009

Status verified

Jan 2012

Primary completion

Nov 30, 2010

Completion

Nov 30, 2010

Study Design

Enrollment

556 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Canakinumab 5 mg + Metformin
  In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
• Experimental: Canakinumab 15 mg + Metformin
  In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
• Experimental: Canakinumab 50 mg + Metformin
  In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
• Experimental: Canakinumab 150 mg + Metformin
  In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose \>200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c \>7.5% were treated with a daily injection of insulin glargine as add-on therapy.
• Placebo Comparator: Placebo + Metformin
  In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).

Primary Outcome Measure

Number of Participants With Adverse Events (AEs), Serious Adverse Events, Death and Clinical Significant AEs During 4 Months (Period II) [ Time Frame: 4 months (Period II) ]

Locations (18)

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