A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED)

A Double-Blind, Randomized, Placebo-Controlled, Single-Dose Crossover Study to Assess the Safety and Tolerability of MK0893 Coadministered With Propranolol Hydrochloride in Patients With Type 2 Diabetes

This study will assess the effect of combined treatment with MK0893 plus propranolol versus placebo plus propranolol on hypoglycemia.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: MK0893; Drug: MK0893-matched Placebo; Drug: Propranolol Hydrochloride (HCL)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant has Type 2 Diabetes (T2DM)
• Participant is either: Not on an oral antihyperglycemic medication for at least 6 weeks; on a single oral antihyperglycemic medication that is not a peroxisome proliferator-activated gamma (PPAR-gamma) agonist (e.g. Avandia); OR on a combination of no more than two antihyperglycemic medications that are not PPAR-gamma) agonists
• Participant has not received insulin for at least 6 months
• Participant has not been treated with a PPAR-gamma agonist for at least 12 weeks
• Participant has been a nonsmoker for at least 6 months
• Female participants who are non-pregnant and highly unlikely to conceive due to surgical sterilization, post-menopausal status, not heterosexually active, or willing to use 2 birth control methods

Exclusion Criteria:

• Participant has a history of stroke, seizures, or neurological disorders
• Participant cannot tolerate insulin or propranolol
• Participant has a history of asthma, emphysema or chronic bronchitis
• Participant is on a weight loss program that is not in the maintenance phase or has been treated with a weight loss medication within 8 weeks of screening
• Participant is on or may require treatment with drugs that affect the immune system or with corticosteroids
• Participant has a history of heart failure or coronary artery disease
• Participant has a history of uncontrolled high blood pressure
• Participant is Human Immunodeficiency (HIV), hepatitis B or hepatitis C positive
• Participant has a history of Type 1 diabetes
• Participant has a history of hypoglycemia unawareness documented by a blood glucose concentration < 55 mg/dL (3.1 mol/L) without symptoms of hypoglycemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propanolol + Placebo > Propanolol + MK0893; Participants received propanolol for 7 weeks. On Day -1 of Period 1 (Study Visit 6), single dose MK0893-matched placebo was added and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol. Following the washout, participants were treated with a single dose of MK0893 on Day 21 (Visit 8).	Drug: MK0893; Single dose of MK0893 1000 mg (ten 100 mg tablets); Drug: MK0893-matched Placebo; Single dose of placebo to MK0893 (ten tablets); Drug: Propranolol Hydrochloride (HCL); Propranolol tablets titrated up to 80 mg three times daily over a four week period. Total treatment was approximately 7 weeks.
Placebo Comparator: Propanolol + MK0893 > Propanolol + Placebo; Participants received propanolol for 7 weeks. On Day -1 of Period 1 (Study Visit 6), single dose MK0893 was added and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol. Following the washout, participants were treated with a single dose of MK0893-matched placebo on Day 21 (Visit 8).	Drug: MK0893; Single dose of MK0893 1000 mg (ten 100 mg tablets); Drug: MK0893-matched Placebo; Single dose of placebo to MK0893 (ten tablets); Drug: Propranolol Hydrochloride (HCL); Propranolol tablets titrated up to 80 mg three times daily over a four week period. Total treatment was approximately 7 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery Time (Rt[65] From Insulin-induced Hypoglycemia	Rt(65) defined as the time to recover from hypoglycemia (blood glucose level of 50 mg/dL) to an arterialized venous blood glucose of 65 mg/dL. At t= -60 minutes on the morning of Day 1 (Visit 6) or Day 22 (Visit 8), a hypoglycemic clamp was used via an increased insulin infusion rate to achieve blood glucose concentrations of 50 mg/dL (2.8 mmol/L) within ~30-90 minutes. At the end of the 30-minute hypoglycemic clamp interval, insulin and glucose infusions were terminated, and the time to recover from hypoglycemia to 65 mg/dL Rt(65) was determined. Rt(65) was followed up to 270 minutes	From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893	Cmax was the maximum or "peak" concentration of MK0893 observed after its administration. Approximate C(ave 8-12) was the MK0893 concentration average over 8-12 hours post-dose and was computed as the Area Under the Curve over 8-12 hours post-dose (AUC [8-12]) ÷ 4	From time of MK0893 administration through 24 hours post-dose
Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893	Plasma concentration of single dose MK0893 was measured from time of administration to 24 hours post-dose and extrapolated out to 32 hours post-dose using the plasma concentration vs. time curve	From time of MK0893 administration through estimated 32 hours post-dose
Number of Participants With An Adverse Event (AE)	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product.	From time of administration of study treatment through end of Post-Study (up to 21 days after administration of last dose of study treatment).
Number of Participants Who Discontinued Study Treatment Due To AEs	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product.	From time of first administration of study treatment to time of last administration of study treatment (up to Day 21)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: May 13, 2009
• First Submitted That Met QC Criteria: May 13, 2009
• First Posted (Estimate): May 15, 2009

Study Record Updates

• Last Update Posted (Estimate): July 3, 2015
• Last Update Submitted That Met QC Criteria: June 8, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: 0893-019; 2009_592