Conditions: Diabetes Mellitus, Type 2
Keywords: type 2 diabetes canakinumab
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 556
Healthy volunteers: no

Brief summary:
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.

Detailed description:

Arms:
arm 1: 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. arm 2: 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. arm 3: 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. arm 4: 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. arm 5: 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).

Interventions: intervention 1: Canakinumab intervention 2: Metformin intervention 3: Placebo
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: Placebo lyophilized cake will be reconstituted and then used to dilute the 25mg or 150mg solutions to make 5mg, 15mg and 50mg injections.

Protocol document: