Clinical trial NCT03235219: A Phase 1b Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of JNJ-64565111 in Participants With Type 2 Diabetes Mellitus
Official title: A Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64565111 in Men and Women With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-08-01
Enrollment: 39
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 Phase 1b study is to assess the safety and tolerability of JNJ-64565111 in adult men and women (of non-child bearing potential) with Type 2 Diabetes Mellitus.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of type 2 diabetes mellitus (T2DM) at least 3 months prior to Screening
* Hemoglobin A1c (HbA1c) greater than or equal to (\>=) 7.0 percent (%) and lesser than or equal to (\<=)9.5% at Screening
* On a stable treatment regimen for at least 3 months prior to Screening of (1) diet and exercise, and/or (2) metformin monotherapy (at a dose of at least 1,000 milligram (mg) per day)
* Body mass index (BMI) ranging from 25 to 40 kilogram per square meter (kg/m\^2) (inclusive), weighing between 75 and 130 kg (inclusive)
* A woman must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta- hCG) at Screening and Day -2
* Blood pressure (measured after the participant is sitting/ resting quietly for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and between 60 and 100 mmHg diastolic, inclusive at Screening (sitting) and Day -2 (supine). If the average of the first triplicate blood pressure assessment is out of range, up to 2 repeated triplicate assessments are permitted

Exclusion Criteria:

* History or current diagnosis of acute or chronic pancreatitis
* Familial or personal history of multiple endocrine neoplasia type 2,familial/non-familial medullary thyroid carcinoma
* Donated blood or blood products or lost a significant amount of blood (\>500 milliliter \[mL\]) within 3 months before the first administration of study drug
* History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
* History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to Day 72
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
measure: Area Under Concentration-Time Curve From Time Zero to the Last Quantifiable Time (AUC [0-last])
timeFrame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD)
measure: Average Concentration Over the Dosing Interval Tau (T) at Steady State (Caverage,ss)
timeFrame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
measure: Minimum Observed Serum Concentration (Cmin)
timeFrame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
measure: Accumulation Ratio
timeFrame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168 hours PD
measure: Area Under Curve over the dosing interval AUC (0-T)
timeFrame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168 hours PD
measure: Apparent Terminal Elimination Half-life (t1/2term)
timeFrame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
measure: Apparent Clearance (CL/F)
timeFrame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
measure: Apparent Volume of Distribution (V/F)
timeFrame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
measure: Terminal Rate Constant (Kel)
timeFrame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
measure: Number of Participants With Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity
timeFrame: First Dose: Predose (Day 1); Second Dose: predose (Day 8) Third Dose: predose (Day 15); Fourth Dose: predose (Day 22), 144, 480, 720, and 1200 hours post-dose.
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
measure: Change From Baseline in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
measure: Change From Baseline in Fasting Lipids
timeFrame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
measure: Change From Baseline for 24-hour Mean Plasma Glucose
timeFrame: Baseline, Day 26
measure: Change From Baseline in C-peptide Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
timeFrame: Baseline, Day 26
measure: Change From Baseline in Total and/or Incremental Plasma Glucose Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
timeFrame: Baseline, Day 26
measure: Change From Baseline in Insulin Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
timeFrame: Baseline, Day 26
measure: Change From Baseline in Glucagon Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
timeFrame: Baseline, Day 26
measure: Change From Baseline in 24-hour Blood Pressure
timeFrame: Baseline and Day 28
measure: Change From Baseline in 24-hour Heart Rate
timeFrame: Baseline and Day 28
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
measure: Change From Baseline Insulin Secretion as Assessed by the Insulinogenic Index
timeFrame: Baseline, Day 26
measure: Change from Baseline in Insulin Secretion as Assessed by Homeostasis Model Assessment of Beta Cell Function (HOMA-%B)
timeFrame: Baseline, Day 26
measure: Change From Baseline in Insulin Sensitivity as Assessed by Matsuda Index
timeFrame: Baseline, Day 26
measure: Change From Baseline in Insulin Sensitivity as Assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-%S)
timeFrame: Baseline, Day 26
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: ProSciento, Inc.
state: California
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: