Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of REMD-477 in Subjects With Type 2 Diabetes Mellitus

Diabetes Clinical Trial

Official title:

A Randomized, Placebo-controlled, Double-blind, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Single and Repeated Subcutaneous (SC) Doses of REMD-477 in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02455011
• Other study ID #: R477-201
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 20, 2015
• Last updated: April 9, 2018
• Start date: September 2015
• Est. completion date: February 2018

Study information

• Verified date: April 2018
• Source: REMD Biotherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, placebo-controlled, double-blind, dose escalation study to evaluate safety, tolerability, PK and PD of single and repeated SC doses of REMD-477 in Type 2 diabetic subjects. The study will be conducted at multiple sites in the United States and will enroll approximately 102 subjects with Type 2 diabetes who are either treatment-naïve, controlled with diet and exercise or treated with oral antidiabetic medications.

Description:

The study will consist of three parts: Part A - Dose Escalation, Part B - Adaptive Dose Cohort, and Part C - REMD-477 in Combination with Metformin. Part A includes 5 cohorts that will be enrolled and dosed sequentially at escalating doses. Each cohort will consist of 12 subjects randomized in a 3:1 (active: placebo) fashion. Part B includes a single dose cohort that will enroll 12 subjects (9 on active treatment and 3 on placebo) with dose level and frequency determined by a Dose Level Review Meeting (DLRM)Committee. Part C includes 2 cohorts of T2DM patients currently treated with metformin alone, and each cohort will consist of 15 subjects (10 on active treatment and 3 on placebo).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: February 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;

• Females of non-child bearing potential must be =1 year post-menopausal (confirmed by a serum follicle-stimulating hormone (FSH) levels = 40 IU/mL) or documented as being surgically sterile, and females of child bearing potential must use two medically acceptable methods of contraception;

• Male subjects must be willing to use clinically acceptable contraception during treatment and for 2 months after the last administration of REMD-477;

• Normal or clinically-acceptable physical examination, laboratory test values, and 12-lead ECG (reporting heart rate and PR, QRS, QT, and QTcF) at screening;

• Body mass index between 23 and 40 kg/m2, inclusive, at screening;

• Diagnosed with Type 2 diabetes as defined by the current American Diabetes Association (ADA) criteria;

• Subjects in Parts A and B only: Treatment-naive, controlled with diet and exercise, or treated with oral antidiabetic medications and willing to wash-out and discontinue oral medications during the study;

• Fasting plasma glucose 126 - 270 mg/dL (7-15 mM), inclusive, at screening and at re-test on Day -1;

• Subjects in Parts A and B only: Screening HbA1c of 7.0-10 % inclusive for subjects not currently taking any oral antidiabetic medications, or 6.5-9.5% for subjects receiving acceptable oral antidiabetic medications;

• Subjects in Part C only: Screening HbA1c of 7.5-10 % inclusive for subjects on stable doses of metformin.

Exclusion Criteria:

• History of drug or alcohol abuse within the last 6 months or a positive illegal drug urine test result;

• History or family history of pancreatic neuroendocrine tumors or multiple endocrine neoplasia;

• History or family history of pheochromocytoma;

• Known or suspected susceptibility to infectious disease (eg, taking immunosuppressive agents or has a documented inherited or acquired immunodeficiency);

• Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C antibodies (HepC Ab);

• Participation in an investigational drug or device trial within 30 days of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known, whichever period is longer;

• Blood donor, or blood loss>300 mL, within 30 days of Day 1;

• Recent use (6 weeks prior to Screening) of thiazolidinediones, >half-maximal dose sulfonylurea agent therapy, or any injectable antidiabetic agents (exenatide and other injectable GLP-1 agonists, insulin and insulin analogs, etc.);

• Other gastrointestinal, cardiac, renal and CNS (i.e. hypoglycemia unawareness) conditions specific to diabetes that would pose additional risk to subject's safety or interfere with the study evaluation, procedures or completion;

• Lipid panel profiles of non-HDL-C (total cholesterol minus HDL-C) >219 mg/dL, LDL-C >189 mg/dL, and/or fasting triglycerides >499 mg/dL;

• Female subject is pregnant or breastfeeding.

Other inclusion and exclusion criteria may apply.

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Biological:
• REMD-477

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
REMD Biotherapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treatment emergent adverse events per subject, including changes in vital signs, physical and neurological examinations, laboratory safety tests and ECGs		141 Days
Secondary	Pharmacokinetic (PK) profile (parameters including maximum observed concentration (Cmax), area under the curve (AUC) serum-concentration, clearance, and half-life (t1/2) after single and repeated SC doses.		141 Days
Secondary	Changes in fasting glucose and insulin levels following single and repeated SC doses of REMD-477.		141 Days
Secondary	Changes in glucose and insulin AUC following a Mixed Meal Tolerance Test.		Day 29, Day 57 and Day 85
Secondary	Incidence of REMD-477 neutralizing and non-neutralizing antibodies		141 Days
Secondary	Incidence of elevated alanine transaminase (ALT) or aspartate transaminase (AST) values >3x the upper limit of normal with concomitant >2x increases in alkaline phosphatase (ALP) and/or >2x total bilirubin.		141 Days
Secondary	Incidence and severity of elevated amylase and lipase values at >2.5x ULN after study treatment		141 Days
Secondary	Geometric mean ratio to baseline over time of AST, ALT, ALP and total bilirubin.		141