A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED)
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT00902161
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will assess the effect of combined treatment with MK0893 plus propranolol versus placebo plus propranolol on hypoglycemia.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Propanolol + Placebo > Propanolol + MK0893 Propranolol Hydrochloride (HCL) 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). Propanolol + MK0893 > Propanolol + Placebo MK0893 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). Propanolol + Placebo > Propanolol + MK0893 MK0893-matched Placebo 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). Propanolol + Placebo > Propanolol + MK0893 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). Propanolol + MK0893 > Propanolol + Placebo MK0893-matched 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). Propanolol + MK0893 > Propanolol + Placebo Propranolol Hydrochloride (HCL) 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).
- Primary Outcome Measures
Name Time Method Recovery Time (Rt[65] From Insulin-induced Hypoglycemia From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes 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
Name Time Method Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893 From time of MK0893 administration through estimated 32 hours post-dose 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) From time of administration of study treatment through end of Post-Study (up to 21 days after administration of last dose of study treatment). 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.Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893 From time of MK0893 administration through 24 hours post-dose 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 \[8-12\]) ÷ 4Number of Participants Who Discontinued Study Treatment Due To AEs From time of first administration of study treatment to time of last administration of study treatment (up to Day 21) 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.