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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00902161
• Other study ID #: 0893-019
• Secondary ID: 2009_592
• Status: Completed
• Phase: Phase 1
• First received: May 13, 2009
• Last updated: June 8, 2015
• Start date: May 2009
• Est. completion date: November 2009

Study information

• Verified date: June 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: November 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• MK0893
Single dose of MK0893 1000 mg (ten 100 mg tablets)
• MK0893-matched Placebo
Single dose of placebo to MK0893 (ten tablets)
• Propranolol Hydrochloride (HCL)
Propranolol tablets titrated up to 80 mg three times daily over a four week period. Total treatment was approximately 7 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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).	Yes
Secondary	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)	Yes