A Safety and Pharmacokinetic Study of CVX-096 in Type 2 Diabetics

Study Overview
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Brief Summary
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The purpose of this study is to determine safety and tolerability of CVX-096 in adult, type 2 diabetic patients.

Official Title
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A Phase 1, Placebo-controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Escalating Subcutaneous Doses Of Cvx-096 In Type 2 Diabetic Adult Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Biological: CVX-096


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and/or female patients (females will be women of non-childbearing potential) with an historical diagnosis of type 2 diabetes mellitus, who are currently being treated with metformin at a dose at or near maximum. Hb A1c between 7-10%. Fasting C-peptide >0.4 nmol/L. Exclusion Criteria: History of clinically significant chronic conditions other than T2DM not well controlled by either diet or medications. Patients with pancreatitis or considered a high risk for pancreatitis. History of contraindications to metformin therapy. Previous treatment with an approved or investigational GLP 1 mimetic.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: CVX-096<br>* Subcutaneous administration of CVX-096 with doses ranging from 0.1 mg up to a maximum of 36 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | AUClast was defined as area under the concentration-time curve from time zero to the time of last measured concentration and calculated by using linear up/log down trapezoidal method. | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 |  | Cohort 1-9: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1; Cohort 10-12: pre-dose, 1 and 6 hours post-dose on Day 1 | 
| Stage 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 8 |  | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8 | 
| Stage 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 22 |  | pre-dose, 1 and 6 hours post-dose on Day 22 | 
| Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 |  | Cohort 1-9: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1; Cohort 10-12: pre-dose, 1 and 6 hours post-dose on Day 1 | 
| Stage 1: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 8 |  | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8 | 
| Stage 2: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 22 |  | pre-dose, 1 and 6 hours post-dose on Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration. | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1 | 
| Stage 1: Apparent Terminal Half-Life (t1/2) of PF-04856883 on Day 8 | Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration. | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8 | 
| Stage 2: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 22 | Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration. | pre-dose, 1 and 6 hours post-dose on Day 22 | 
| Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | MRT is defined as AUMC(0 - inf) divided by AUC(0 - inf), where AUMC(0 - inf) is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method and AUC(0 - inf) is the area under the concentration-time curve extrapolated to infinity. | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1 | 
| Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug apparent oral clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1 | 
| Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | AUC(0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It was calculated as AUC (0-t) plus (last measurable concentration divided by apparent terminal elimination rate constant). | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1 Type 2 diabetes CVX-096 diabetes mellitus, adult-onset diabetes mellitus, non-insulin dependent