Back to resultsA Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK0893
MK0893-matched Placebo
Propranolol Hydrochloride (HCL)
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Propanolol + Placebo > Propanolol + MK0893
Propanolol + MK0893 > Propanolol + Placebo
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00902161
Brief Title
A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED)
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
November 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will assess the effect of combined treatment with MK0893 plus propranolol versus placebo plus propranolol on hypoglycemia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Propanolol + Placebo > Propanolol + MK0893
Arm Type
Experimental
Arm Description
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).
Arm Title
Propanolol + MK0893 > Propanolol + Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
MK0893
Intervention Description
Single dose of MK0893 1000 mg (ten 100 mg tablets)
Intervention Type
Drug
Intervention Name(s)
MK0893-matched Placebo
Intervention Description
Single dose of placebo to MK0893 (ten tablets)
Intervention Type
Drug
Intervention Name(s)
Propranolol Hydrochloride (HCL)
Intervention Description
Propranolol tablets titrated up to 80 mg three times daily over a four week period. Total treatment was approximately 7 weeks.
Primary Outcome Measure Information:
Title
Recovery Time (Rt[65] From Insulin-induced Hypoglycemia
Description
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
Time Frame
From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893
Description
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
Time Frame
From time of MK0893 administration through 24 hours post-dose
Title
Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893
Description
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
Time Frame
From time of MK0893 administration through estimated 32 hours post-dose
Title
Number of Participants With An Adverse Event (AE)
Description
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.
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).
Title
Number of Participants Who Discontinued Study Treatment Due To AEs
Description
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.
Time Frame
From time of first administration of study treatment to time of last administration of study treatment (up to Day 21)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED)
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