Study to Evaluate Safety, Tolerability, Pharmacokinetics & Pharmacodynamics of JTT-662 in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of JTT-662 administered once daily for 28 days in subjects with Type 2 diabetes mellitus (T2DM) who are receiving metformin monotherapy

Official Title
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Single-blind, Randomized, Placebo-controlled, Multiple Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JTT-662 Administered for 28 Days in Subjects With Type 2 Diabetes Mellitus on Metformin Monotherapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: JTT-662
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of T2DM for at least 12 weeks prior to the Screening Visit Currently treated with a stable oral dose of metformin monotherapy for at least 12 weeks prior to the Screening Visit and until Day -3 Have a glycosylated hemoglobin (HbA1c) value of between 6.5% and 10.0% at the Screening Visit Have a fasting plasma glucose (FPG) value of no more than 280 mg/dL at the Screening Visit and on Day -3 Body Mass Index (BMI) of 25 to 40 kg/m2 (inclusive) Exclusion Criteria: Known medical history or presence of Type 1 diabetes mellitus, Maturity Onset Diabetes of the Young or secondary forms of diabetes Known medical history or presence of diabetic complications Have taken anti-diabetic medications (other than metformin) or medications that act mainly in the gastrointestinal tract (e.g., orlistat, acarbose) within 12 weeks prior to the Screening Visit or from the Screening Visit to Day -3 Have uncontrolled hypertension (systolic blood pressure of at least 160 mmHg or diastolic blood pressure of at least 95 mmHg) at the Screening Visit Have impaired renal function (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JTT-662 5 mg<br>JTT-662 5 mg orally once daily from Day 1 to Day 28, after a single dose of placebo on Day -1 | Drug: JTT-662<br>* Active drug tablets containing JTT-662<br>|
| Experimental: JTT-662 10 mg<br>JTT-662 10 mg orally once daily from Day 1 to Day 28, after a single dose of placebo on Day -1 | Drug: JTT-662<br>* Active drug tablets containing JTT-662<br>|
| Experimental: JTT-662 20 mg<br>JTT-662 20 mg orally once daily from Day 1 to Day 28, after a single dose of placebo on Day -1 | Drug: JTT-662<br>* Active drug tablets containing JTT-662<br>|
| Placebo Comparator: Placebo<br>Placebo orally once daily from Day -1 to Day 28 | Drug: Placebo<br>* Placebo tablets matching in appearance to the active drug tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment-emergent Adverse Events | Treatment-emergent adverse event is defined as any adverse event (untoward medical experience occurring to a subject whether or not it is related to the study drug) with an onset date/time at/after the placebo dosing on Day -1. | 6 Weeks (from Day -1 to the follow-up visit on Day 42) | 
| Number of Stools and Type of Stools Based on Bristol Stool Chart | Number of occurrences for each stool type was reported based on their type assessed from Bristol Stool Chart. The Bristol Stool Chart was used to assess the stool shape using a 7-point scale. Where, Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation while a score of 6 or 7 indicates diarrhea. | 7 Weeks (from Day -6 to the follow-up visit on Day 42) | 
| Trough Concentrations of JTT-662 in Plasma on Days 1, 7, 10, 14, 15, 21 and 28 | Trough plasma concentration is the measured concentration at the end of a dosing interval at steady state (taken directly before next administration). Blood samples were collected at specific timepoints to measure trough plasma concentrations of JTT-662 in the subjects randomized to JTT-662 treatment groups. | 28 Days | 
| Change From Baseline in AUEC0-4 for Plasma Postprandial Glucose (PPG) Compared to Placebo on Days 1, 14 and 28 | Change from baseline in the AUEC0-4 (area under the observed effect-time curve from the start of breakfast until the 4 hour time point) for PPG were calculated using the corresponding Day -1 value as baseline and compared to the placebo values. Negative values represent greater reduction in PPG from baseline values compared to placebo. | Days 1, 14 and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JTT-662, Diabetes, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics