A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED)
This study has been completed.
Sponsor:
Merck
Information provided by (Responsible Party):
Merck
ClinicalTrials.gov Identifier:
NCT00902161
First received: May 13, 2009
Last updated: April 10, 2012
Last verified: April 2012
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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:
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 More Information
No publications provided
| Responsible Party: | Merck |
| 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 May 23, 2013