A Phase IIA Study of BMS-512148 to Assess Safety, Exposure, and Biological Effects in Stable Type 2 Diabetic Subjects

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Double-blind, Placebo-controlled, Randomized, Multiple-dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Bms-512148 in Diabetic Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00162305
• Other study ID #: MB102-003
• Status: Completed
• Phase: Phase 2
• First received: September 9, 2005
• Last updated: October 26, 2016
• Start date: April 2005
• Est. completion date: August 2005

Study information

• Verified date: October 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical research study is to assess the safety of, exposure to, and biological effects of BMS-512148 in stable Type 2 diabetic subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: August 2005
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Established diagnosis of Type 2 diabetes mellitus, who are treated with metformin or diet alone (drug naive).

• Fasting glucose (FG) < - 240 mg/dL, while on metformin or antidiabetic diet alone.

• HbA1c (Hemoglobin A1c) in the range of 6.0-10.0%

Exclusion Criteria:

• Women of childbearing potential

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• BMS-512148
Capsules, Oral, 100 mg, Once daily, 14 days.
• BMS-512148
Capsules, Oral, 25 mg, Once daily, 14 days.
• BMS-512148
Capsules, Oral, 5 mg, Once daily, 14 days.
• Placebo
Capsules, Oral, 0 mg, Once daily, 14 days.

Locations

Country	Name	City	State
United States	Local Institution	Fort Lauderdale	Florida
United States	Local Institution	Miami	Florida
United States	Local Institution	New Orleans	Louisiana
United States	Local Institution	Orlando	Florida
United States	Local Institution	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

References & Publications (1)

Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther. 2009 May;85(5):513-9. doi: 10.103 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the safety and tolerability of multiple oral doses of BMS-512148 administered alone or concomitantly with metformin in diabetic subjects	Adverse event monitoring, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments	14 days	Yes
Secondary	To assess the PK of BMS-512148 and its pharmacologically active metabolite, BMS-511926, when BMS-512148 is administered alone or concomitantly with metformin	Exposure to BMS-512148 and BMS-511926	14 days	No
Secondary	To assess the pharmacodynamic effect of BMS-512148, administered alone or concomitantly with metformin, on serum and urine markers of glucose homeostasis	Fasting and post-prandial serum glucose, serum fructosamine, serum insulin, and serum C-peptide and urinary glucose and urinary calcium	14 days	No
Secondary	To assess the effect of BMS-512148, administered alone or concomitantly with metformin, on safety markers in urine	calcium, magnesium, sodium, potassium, phosphate, chloride, uric acid, oxalate, citrate, total protein, albumin, osmolality, deoxypyridinoline (D-pyr) cross-links, C-telopetide (CTX), N-acetyl-ß- D-glucoasaminidase (NAG), and ß2-microglubulin (ß2-MG)	14 days	Yes
Secondary	To assess the effect of BMS-512148, administered alone or concomitantly with metformin, on the following safety markers in serum	Serum osteocalcin, parathyroid hormone (PTH), 25-Vitamin D, and 1,25-Vitamin D	14 days	Yes
Secondary	To assess the effect of BMS-512148 administered alone or concomitantly with metformin on the percent inhibition of renal glucose reabsorption	Percent inhibition of renal glucose resorption over each 0-4 h, 4-8 h, and 8-12 h post-dose interval calculated from the amount of renally filtered glucose and the amount of glucose excreted in the urine for each collection interval.	14 days	No
Secondary	To assess the effects of BMS-512148 on the PK of metformin in diabetic subjects.	Exposure to metformin	14 days	No
Secondary	To identify potential biomarkers in both urine and blood	Serum and urine for metabonomic assessment	14 days	No

External Links

•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm
•   MB102-003 _CSR_synopsis