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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00902161
First received: May 13, 2009
Last updated: April 10, 2012
Last verified: April 2012
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: MK0893
Drug: MK0893-matched Placebo
Drug: Propranolol Hydrochloride (HCL)
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Recovery Time (Rt[65] From Insulin-induced Hypoglycemia [ Time Frame: From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893 [ Time Frame: From time of MK0893 administration through 24 hours post-dose ] [ Designated as safety issue: No ]

    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


  • Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893 [ Time Frame: From time of MK0893 administration through estimated 32 hours post-dose ] [ Designated as safety issue: No ]
    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

  • Number of Participants With An Adverse Event (AE) [ Time Frame: From time of administration of study treatment through end of Post-Study (up to 21 days after administration of last dose of study treatment). ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued Study Treatment Due To AEs [ Time Frame: From time of first administration of study treatment to time of last administration of study treatment (up to Day 21) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 22
Study Start Date: April 2009
Study Completion Date: November 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00902161

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00902161     History of Changes
Other Study ID Numbers: MK-0893-019, 2009_592
Study First Received: May 13, 2009
Results First Received: April 10, 2012
Last Updated: April 10, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Propranolol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vasodilator Agents

ClinicalTrials.gov processed this record on July 28, 2014