Clinical trial NCT00605475: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Type 2 Diabetes
Official title: A Multi Center, Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 Administered Intravenously to Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus
Canakinumab
ACZ885
IL-1B antagonist
metformin
glycemic control
insulin sensitivity
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-01-31
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate, in patients with Type 2 Diabetes Mellitus, whether Canakinumab can lower Glycosylated hemoglobin / hemoglobin A1c (HbA1c) and/or peak glucose levels in response to an oral glucose tolerance test (OGTT).


Eligibility criteria: Inclusion Criteria:

* Male or female patients aged 18 to 70 years, with type 2 diabetes mellitus (non-insulin dependent diabetes) for at least 6 months prior to study start
* HbA1c between 7.0 and 9.5%
* On stable dose metformin monotherapy
* Stable body weight

Exclusion Criteria:

* Poorly controlled type 2 diabetes (very low or very high blood sugar levels, or other indicators of poor control)
* Acute infections prior to dosing
* Patients with type 1 diabetes (insulin-dependent diabetes)
* Taking diabetes medication (other than metformin)

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
timeFrame: Baseline, Day 28, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)
measure: Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT )
timeFrame: Baseline, Day 28, Day 84
Secondary outcomes:
measure: Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT)
timeFrame: Baseline, Day 28, Day 84
measure: Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
timeFrame: Baseline, Day 28, Day 84
measure: Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )
timeFrame: Baseline, Day 28, Day 84
measure: Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test
timeFrame: Baseline, Day 28, Day 84
measure: Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT)
timeFrame: Baseline, Day 28, Day 84
measure: Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours
timeFrame: Day 28, Day 84
measure: Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours
timeFrame: Day 28, Day 84
measure: Insulin Sensitivity Index ( ISI ) at Day 28, Day 48
timeFrame: Day 28, Day 84
measure: Insulinogenic Index, 0 - 30 Minutes
timeFrame: Day 28, Day 84
measure: Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT )
timeFrame: Baseline, Day 28, Day 84
measure: Mean Change From Baseline in Peak Plasma Fructosamine Level
timeFrame: Baseline, Day 14, Day 28, Day 56, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)
measure: Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR)
timeFrame: Baseline, Day 28, Day 84
measure: β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β )
timeFrame: Baseline, Day 28, Day 84
measure: Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency
timeFrame: Baseline to End of Study (56[+/-2] and 168 [+/- 5] days after dosing for Cohort 1 and Cohorts 2-4, respectively)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Research Medical Testing
state: Arkansas
city: Miami
country: United States
facility: Allied Research International - Cetero Research Miami
state: Florida
city: Miami
country: United States
facility: Elite Research Institute Miami
state: Florida
city: MD
country: United States
facility: International Research Center Towson
state: Maryland
city: Portland
country: United States
facility: Covance Clinical Research Unit Inc
state: Oregon
city: NW Tacoma
country: United States
facility: Charles River Clinical Services
state: Washington
city: Berlin
country: Germany
facility: Novartis Investigator Site
city: Kiel
country: Germany
facility: Novartis Investigator Site
city: Moenchengladbach
country: Germany
facility: Novartis Investigator Site
city: Munich
country: Germany
facility: Novartis Investigator Site
city: Neuss
country: Germany
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersberg
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis investigator site
name: NOVARTIS
role: PRINCIPAL_INVESTIGATOR
References: