The primary objective of this study is to evaluate the effect of 12-week treatment with JNJ-16269110 on the glycated hemoglobin (HbA1c) concentration in subjects with T2DM.Additional objectives are to evaluate the effect of JNJ-16269110 on:1.…
ID
Source
Brief title
Condition
- Diabetic complications
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy parameter will be HbA1c
Secondary outcome
Fasting blood glucose concentrations
Fasting plasma insulin, C-peptide and glucagon
In-Clinic Meal Mixed Tolerance Test (MMTT) (selected centres - approximately
120 patients)
Gastrointestinal hormones (GLP-1, PYY)
Insulin sensitivity
Beta cell function
Homeostatic Model Assessment, HOMA2 (%S and %R)
Self Monitored Blood Glucose (SMBG)
· Self Monitored Fasting Blood Glucose (SMFBG)
· 7-point blood glucose profiles
Lipids and lipoproteins
BMI and Waist to Hip Ratio
Weight
Quality of life - DTSQs/DTSQc/ IWQOL-Lite questionnaires
Treatment satisfaction questions
SAFETY EVALUATIONS
Adverse events
Physical examination and vital signs
12- lead ECG
Lab safety parameters
Background summary
The microsomal triglyceride transfer protein (MTP) inhibitor JNJ-16269110, when
administered twice daily after a meal to healthy subjects for 2 and 4 weeks,
was shown to increase fasting and postprandial plasma glucagon-like peptide 1
(GLP-1) and peptide tyrosine tyrosine (PYY) levels and in addition caused
weight loss. Those observations (increased GLP-1 expected to improve
glucose-dependent insulin secretion, and weight loss improving insulin
sensitivity) provided the rationale to investigate this new experimental drug
in subjects with Type 2 Diabetes Mellitus (T2DM).
Study objective
The primary objective of this study is to evaluate the effect of 12-week
treatment with JNJ-16269110 on the glycated hemoglobin (HbA1c) concentration in
subjects with T2DM.
Additional objectives are to evaluate the effect of JNJ-16269110 on:
1. Fasting plasma glucose, the glycemic excursions and insulin secretion
measured after a standardized, in-clinic mixed meal tolerance test (MMTT)
2. Fasting concentrations and postprandial responses of the gastrointestinal
and pancreatic hormones to the standardized mixed meal
3. Insulin sensitivity and beta cell function based on plasma glucose, insulin
and C-peptide responses to the MMTT and evaluated by HOMA2
4. Self-monitored blood glucose (SMBG) by means of 7-point glucose measurements
and symptomatic hypoglycemia
5. Body weight, BMI and waist to hip ratio
6. Fasting plasma lipids including total cholesterol (TC), triglycerides (TG),
VLDL, LDL, HDL, and lipoproteins (ApoB100, ApoB48 en ApoA1) and postprandial TG
excursion after MMTT.
7. Blood pressure
8. Safety and tolerability including
· Vitamins (retinol, beta-carotene, 25-hydroxy-cholecalciferol,
alpha-tocopherol and vitamin K) concentrations and coagulation parameters (INR,
aPTT),
· Essential Fatty acids and non-esterified fatty acid (NEFA) concentration
· Liver function tests
· Symptomatic hypoglycemia.
9. Assess pharmacokinetic exposure of JNJ-16269110 to explore plasma
exposure-response relationships and to develop a population pharmacokinetic
model
10. Evaluate quality of life using Diabetes Treatment Satisfaction
Questionnaires status and change (DTSQs and DTSQc) and Impact of Weight on
Quality of Life Questionnaire-Lite version (IWQOL-Lite)
11. Evaluate overall satisfaction with study drug.
Study design
This is a randomized, double-blind, placebo-controlled, parallel-group,
multi-center, international phase IIa/b study involving 4 groups of 80 T2DM
subjects (n=320 in total) who are on monotherapy with metformin. Subjects will
be randomized to one out of the 4 treatment groups and will receive either one
out of 3 different doses of MTP inhibitor or placebo for a period of 12 weeks.
· Group 1 (N= 80)
Subjects will be dosed with 5 mg bid for 12 weeks
· Group 2 (N= 80)
Subjects will be dosed with 10 mg bid for 12 weeks
· Group 3 (N=80)
Subjects will be dosed with 15 mg bid for 12 weeks
· Group 4 (N=80)
Subjects will be dosed with placebo bid for 12 weeks
The study consists of a 28-day Screening period, a Baseline visit (Day -1), the
Treatment period (Days 1 to 84) and a Follow-up visit scheduled 10 to 14 days
after the last dose administration.
Study burden and risks
Burden:
The 10 visits will last approximately 16 hours in total.
The entire study lasts approximately 18 weeks.
Blood will be drawn at 10 visit. Throughout the entire study a maximum volume
of 381.3 ml blood will be drawn.
Risks:
JNJ16269110 can cause unwanted effects, called side effects. These are listed
in the patient information.
The following measuress are taken to minimize the risks:
An extensive screening visit is planned, before randomization. During the study
the patient will be followed closely, including follow up of possible adverse
events.
If the glucose level during the study is too high during 2 measurements, the
doctor adapts the metformin dose or give another medication (not
investigational but marketed) to treat type 2 diabetes.
Postbus 90240
5000 LT Tilburg
Nederland
Postbus 90240
5000 LT Tilburg
Nederland
Listed location countries
Age
Inclusion criteria
1. Men or women with a history of T2DM and treated with a stable dose of metformin for at least 2 months prior to screening.
2. Between 18 and 70 years of age, inclusive
3. Women must be
* postmenopausal;
* or surgically incapable of childbearing
* or if sexually active, be practicing an effective method of birth
control
* sexually abstinent.
* Women of childbearing potential must be practicing an acceptable method
of birth control and have a negative pregnancy test before and during the trial
4. BMI between 25 and 45 kg/m2, inclusive
5. HbA1c between 7% and 10%, inclusive
6. Fasting plasma glucose not exceeding 13.3mmol/L
Exclusion criteria
1. Diabetes other than type 2 diabetes mellitus.
2. Treatment with oral anti-diabetic agents (other than metformin) or insulin
during the 12 weeks before baseline visit.
3. Prior exposure or known contraindication or hypersensitivity to
JNJ-16269110.
4. History of intolerance to or hypersensitivity to sulfonylurea or sitagliptin.
5. History of an uninterrupted period of insulin therapy for >1 month period
within 1 year prior to baseline visit.
6. Likelihood of requiring treatment during the study period with antidiabetic
medications
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-000031-26-NL |
| Other | N/A |
| CCMO | NL19353.003.07 |