A Study to Assess the Safety, Tolerability, and Effects of MK-0974 (Telcagepant) on Exercise Tolerance in Patients With Stable Angina (MK-0974-014)

NCT01294709 | Completed Phase 1 Results

• 1 other identifier: 0974-014
• Study Type: interventional
• Target: 64
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assess the safety of telcagepant in coronary artery disease (CAD) participants with stable angina during exercise treadmill testing and evaluate whether calcitonin gene-related peptide (CGRP) receptor antagonism by telcagepant reduces exercise tolerance in these participants. Primary hypothesis is that telcagepant does not significantly decrease exercise duration compared to placebo, as measured by a treadmill exercise test; that is, the true treatment difference in exercise duration (MK-0974 - Placebo) \>= -60 seconds.

Conditions

Angina Pectoris; Coronary Heart Disease; Calcitonin Gene-related Peptide Receptor

Keywords

angina pectoris; coronary artery disease; calcitonin gene-related peptide; exercise tolerance,

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Clinical Adverse Events (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 product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A clinical AE was an AE reported as a result of a clinical examination or reported by the participant.

  Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2

• Number of Participants With Laboratory Adverse Events

  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 product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A laboratory AE was an AE reported as a result of a laboratory assessment or test.

  Up to 10 days post dose in Period 1 and up to 14 days post dose in Period 2

• Total Exercise Duration on the Treadmill Test

  Bruce (and Modified Bruce) Protocol was used to assess the exercise duration on a treadmill. This protocol consists of a standardized gradual incremental increase in external workload every 3 minutes while the participant's electrocardiogram (ECG), symptoms, and arm blood pressure were continuously monitored. Regardless of whether the participant believed he or she could continue, the test was discontinued upon evidence of chest discomfort, severe shortness of breath, dizziness, fatigue, ST-segment depression of greater than 2 mm, a fall in systolic blood pressure exceeding 10 mmHg, or the development of a ventricular tachyarrhythmia

  2.5 to approximately 2.75 hours post dose of each treatment period

Secondary Outcomes (2)

• ST Segment Depression at Peak Exercise

  2.5 to approximately 2.75 hours post dose of each treatment period

• Time to 1 mm ST Segment Depression

  2.5 to approximately 2.75 hours post dose of each treatment period

Study Arms (2)

Telcagepant/ Placebo

EXPERIMENTAL

Participants receive single oral dose of 600 mg (two 300 mg capsules or two bioequivalent 280 mg tablets) or 900 mg telcagepant (three 300 mg capsules) in Period 1 and single oral dose of two capsules or tablets of placebo for telcagepant (or three capsules of placebo for telcagepant) in Period 2 of the crossover. Each treatment period is separated by a washout of 96-240 hours.

Drug: telcagepant; Drug: Placebo to telcagepant

Placebo/Telcagepant

EXPERIMENTAL

Participants receive single oral dose of two capsules or tablets of placebo for telcagepant (or three capsules of placebo for telcagepant) in Period 1 and a single oral dose of 600 mg (two 300 mg capsules or two bioequivalent 280 mg tablets) or 900 mg telcagepant (three 300 mg capsules) in Period 2 of the crossover. Each treatment period is separated by a washout of 96-240 hours.

Drug: telcagepant; Drug: Placebo to telcagepant

Interventions

telcagepant DRUG

Also known as: MK-0974

Placebo/Telcagepant; Telcagepant/ Placebo

Placebo to telcagepant DRUG

Placebo/Telcagepant; Telcagepant/ Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has clinically documented stable coronary artery disease as demonstrated by coronary angiography, echocardiogram, or stress test, etc., or participant is on stable doses of current medication for the treatment of coronary artery disease for a minimum of 30 days.
• Participant has a history of stable angina (chronic stable angina pectoris that is triggered by physical effort and relieved by rest and/or sublingual nitroglycerin) for at least 3 months prior to study start, with no intervening symptoms of unstable angina.
• Participant is able to demonstrate reproducibly positive exercise tests by completing treadmill tests on 2 separate days, within 1-8 days.
• Participant agrees to refrain from drinking alcohol from 24 hours prior to study drug administration, on study procedure days, and until release from the study facility.
• Participants agrees to refrain from smoking from midnight before study procedures until study procedures are complete for the day.
• Participant has no clinically significant abnormality on screening laboratory safety assessment.
• Participant agrees to refrain from unaccustomed strenuous physical activity from the prestudy (screening) visit, throughout the study, and until the post-study visit.

You may not qualify if:

• Participant is pregnant (positive serum beta-human chorionic gonadotropin \[β-hCG\] test at prestudy), breast-feeding, or is a female expecting to conceive within the projected duration of the study. Postmenopausal women who are currently using hormone replacement therapy are excluded from participation in the study.
• Participant has heart rate-corrected QT interval (QTc) (Bazett) \> 500 ms on resting ECG.
• Participant has uncontrolled high blood pressure at prestudy screening.
• Participant has a baseline heart rate of \<40 or \>96 beats per minute at screening.
• Participant has unstable angina, hypertrophic cardiomyopathy, valvular heart disease, congenital cardiac defect, severe aortic stenosis, class III or IV heart failure.
• Participant has diabetes and is, in the opinion of the investigator, unable to comply with the pre-and post-dosing fasting requirements of the study due to risks of hypoglycemia.
• Participant is unable to withhold acetohexamide, chlorpropamide, glimepride, glimepiride and pioglitazone, glimepride and rosiglitazone, glipizide, glipizide and metformin, glyburide, glyburide and metformin, tolazamide, tolbutamide, or any other medication, that in the opinion of the investigator is likely to result in hypoglycemia within 8 hours of dosing.
• Participant has had myocardial infarction or coronary revascularization within the prior 2 months.
• Participant has acute myocarditis or pericarditis.
• Participant is obese, with adipose tissue which may interfere with ECG interpretation, or in the opinion of the investigator, whose obesity puts the participant at medical risk.
• Participant has clinically significant hypokalemia or hypomagnesemia.
• Participant has a history of any illness that, in the opinion of the investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
• Participant must not have taken any of the following medications in the time frame specified: Participant is unable to refrain from or anticipates the use of any herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatments), until the post-study visit; participant is unable to refrain from taking a drug metabolized by cytochrome P450 3A4 (CYP3A4) until at least 48 hours post dose (the exact length of time a specific drug metabolized by CYP3A4 is withheld is dependent on the therapeutic index of the drug and the extent to which it is metabolized by CYP3A4); participant consumes excessive amounts of alcohol which, in the opinion of the investigator, puts the participant at medical risk by participating in the study (participant has clinical \[e.g., enlarged liver\] or laboratory evidence \[e.g., elevated alanine aminotransferase (ALT)\], of chronic alcoholism or drug abuse, in the opinion of the investigator); participants is currently a regular user (including: recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 6 months; participant has taken potent CYP3A4 inhibitors, including but not limited to cyclosporine, systemic (oral/intravenous) itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, nefazodone, human immunodeficiency virus (HIV) protease inhibitors within 1 month prior to dosing with MK-0974 or placebo and throughout the study period; participant has taken moderate CYP3A4 inhibitors, including but not limited to verapamil, diltiazem, fluconazole, fluvoxamine, fluoxetine, aprepitant within 2 weeks prior to dosing with MK-0974 or placebo and throughout the study period; participant has taken potent CYP3A4 inducers, including but not limited to rifampicin, rifabutin, carbamazepine, phenytoin, barbiturates, systemic glucocorticoids (replacements and inhaled are permitted), nevirapine, efavirenz, pioglitazone, primidone, St. John's wort within 1 month prior to dosing MK-0974 or placebo and throughout the study period; participant has taken triptans, ergot alkaloids within 48 hours prior to dosing MK-0974 or placebo and throughout the study period; participant has taken digoxin, medications that prolong QTc interval such as Class IA and Class III anti-arrhythmics (quinidine, procainamide, amiodarone, sotalol, etc), Seldane (terfenadine), Hismanal (astemizole), Propulsid (cisapride) within 1 month prior to dosing MK-0974 or placebo and throughout the study period; participant has received an investigational medication within 4 weeks prior to the prestudy (screening) visit.
• Participant has a history of multiple and/or severe allergies, or has had an anaphylactic reaction or intolerability to prescription or non-prescription drugs or food.
• There is any concern by the investigator regarding the safe participation of a participant in the study, or for any other reason the investigator considers the participant inappropriate to participate in the study.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Chaitman BR, Ho AP, Behm MO, Rowe JF, Palcza JS, Laethem T, Heirman I, Panebianco DL, Kobalava Z, Martsevich SY, Free AL, Bittar N, Chrysant SG, Ho TW, Chodakewitz JA, Murphy MG, Blanchard RL. A randomized, placebo-controlled study of the effects of telcagepant on exercise time in patients with stable angina. Clin Pharmacol Ther. 2012 Mar;91(3):459-66. doi: 10.1038/clpt.2011.246. Epub 2012 Jan 25.

  PMID: 22278333 RESULT

MeSH Terms

Conditions

Angina Pectoris; Coronary Disease; Coronary Artery Disease

Interventions

telcagepant

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases

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 Director

  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: February 10, 2011
• First Posted: February 11, 2011
• Study Start: February 12, 2008
• Primary Completion: February 28, 2009
• Study Completion: March 13, 2009
• Last Updated: October 18, 2018
• Results First Posted: September 10, 2014

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share