NCT00902161

Brief Summary

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

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at below P25 for phase_1 type-2-diabetes-mellitus

Timeline
Completed

Started May 2009

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2009

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

May 13, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 15, 2009

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2009

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2009

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

May 8, 2012

Completed
Last Updated

July 3, 2015

Status Verified

June 1, 2015

Enrollment Period

5 months

First QC Date

May 13, 2009

Results QC Date

April 10, 2012

Last Update Submit

June 8, 2015

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (4)

  • 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

  • Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893

    From time of MK0893 administration through estimated 32 hours post-dose

  • 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).

  • Number 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)

Study Arms (2)

Propanolol + Placebo > Propanolol + MK0893

EXPERIMENTAL

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: MK0893Drug: MK0893-matched PlaceboDrug: Propranolol Hydrochloride (HCL)

Propanolol + MK0893 > Propanolol + Placebo

PLACEBO COMPARATOR

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: MK0893Drug: MK0893-matched PlaceboDrug: Propranolol Hydrochloride (HCL)

Interventions

MK0893DRUG

Single dose of MK0893 1000 mg (ten 100 mg tablets)

Propanolol + MK0893 > Propanolol + PlaceboPropanolol + Placebo > Propanolol + MK0893
MK0893-matched PlaceboDRUG

Single dose of placebo to MK0893 (ten tablets)

Propanolol + MK0893 > Propanolol + PlaceboPropanolol + Placebo > Propanolol + MK0893
Propranolol Hydrochloride (HCL)DRUG

Propranolol tablets titrated up to 80 mg three times daily over a four week period. Total treatment was approximately 7 weeks.

Propanolol + MK0893 > Propanolol + PlaceboPropanolol + Placebo > Propanolol + MK0893

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

N-((4-(1-(3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl)ethyl)phenyl)carbonyl)-beta-alaninePropranolol

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic Compounds

Results Point of Contact

Title
Senior Vice President, Global Clinical Development
Organization
Merck Sharp & Dohme Corp
ClinicalTrialsDisclosure@merck.com
1-800-672-6372

Study Officials

  • Medical Monitor

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 13, 2009

First Posted

May 15, 2009

Study Start

May 1, 2009

Primary Completion

October 1, 2009

Study Completion

November 1, 2009

Last Updated

July 3, 2015

Results First Posted

May 8, 2012

Record last verified: 2015-06