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Telcagepant (MK-0974) Long-Term Safety Study in Adult Participants With Acute Migraine (MK-0974-012)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00443209
Recruitment Status : Completed
First Posted : March 5, 2007
Results First Posted : August 18, 2014
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Migraine
Interventions Drug: Telcagepant 300 mg soft gel capsules
Drug: Telcagepant 280 mg tablets
Drug: Rizatriptan 10 mg tablets
Drug: Placebo to telcagepant capsules
Drug: Placebo to telcagepant tablets
Drug: Placebo to rizatriptan tablets
Enrollment 1068
Recruitment Details  
Pre-assignment Details The trial was considered to have achieved completion as defined by the treatment of 100 participants for 12 months.
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Hide Arm/Group Description Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months. Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months.
Period Title: Months 1 to 12 Treatment Period
Started 712 356
Treated 641 313
Completed 367 [1] 202 [1]
Not Completed 345 154
Reason Not Completed
Adverse Event             22             11
Protocol Violation             14             7
Lack of Efficacy             50             11
Lack of Qualifying Event             1             1
Lost to Follow-up             36             15
Physician Decision             8             4
Pregnancy             3             4
Trial Terminated             43             23
Withdrawal by Subject             95             34
Missing             2             1
Not Treated             71             43
[1]
Trial terminated used for participants not completing 12 months of treatment due to trial completion
Period Title: Months 13 to 18 Treatment Period
Started 186 [1] 86 [2]
Completed 87 [3] 39 [3]
Not Completed 99 47
Reason Not Completed
Adverse Event             1             0
Protocol Violation             1             0
Lack of Efficacy             1             0
Lost to Follow-up             2             2
Trial Terminated             87             43
Withdrawal by Subject             7             2
[1]
The Months 13 to 18 Treatment Period.was optional. 181 participants chose not to continue.
[2]
The Months 13 to 18 Treatment Period was optional. 116 participants chose not to continue.
[3]
Trial terminated used for participants not completing 18 months of treatment due to trial completion
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg Total
Hide Arm/Group Description Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months. Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months. Total of all reporting groups
Overall Number of Baseline Participants 641 313 954
Hide Baseline Analysis Population Description
Baseline Analyis Population consisted of All Treated Participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 641 participants 313 participants 954 participants
42.5  (10.9) 41.9  (11.1) 42.3  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 641 participants 313 participants 954 participants
Female
502
  78.3%
237
  75.7%
739
  77.5%
Male
139
  21.7%
76
  24.3%
215
  22.5%
1.Primary Outcome
Title Percentage of Participants With At Least One Triptan-Related Adverse Experience (AE)
Hide Description Triptan-related AEs are defined as: chest pain, chest tightness, asthenia, paraesthesia, dysaesthesia or hyperaesthesia. Participants were monitored for triptan-related AEs for 14 days after any dose of study drug.
Time Frame Within 14 days of any dose of study drug (Up to 18.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The All-Patients-As-Treated (APAT) population consisted of all participants who received at least one dose of study drug.
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Hide Arm/Group Description:
Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months.
Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months.
Overall Number of Participants Analyzed 641 313
Measure Type: Number
Unit of Measure: Percentage of Participants
5.0 11.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Telcagepant 280 mg/300 mg, Rizatriptan 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettenen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-10.4 to -2.6
Estimation Comments Treatment Difference was compared using the Miettinen and Nurminen (MN) method.
2.Primary Outcome
Title Percentage of Participants With At Least One Clinical AE
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study 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 is temporally associated with the use of the study product, is also an AE. A clinical AE was an AE reported as a result of a clinical examination. Participants were monitored for clinical AEs for 14 days after any dose of study drug.
Time Frame Within 14 days of any dose of study drug (Up to 18.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The APAT population consisted of all participants who received at least one dose of study drug.
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Hide Arm/Group Description:
Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months.
Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months.
Overall Number of Participants Analyzed 641 313
Measure Type: Number
Unit of Measure: Percentage of Participants
58.7 63.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Telcagepant 280 mg/300 mg, Rizatriptan 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -5.2
Confidence Interval (2-Sided) 95%
-11.7 to 1.4
Estimation Comments Treatment Difference was compared using the MN method.
3.Primary Outcome
Title Percentage of Participants With At Least One Laboratory AE
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study 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 is temporally associated with the use of the study product, is also an AE. A laboratory AE was an AE reported as a result of a laboratory assessment or test. Participants were monitored for laboratory AEs for 14 days after any dose of study drug.
Time Frame Within 14 days of any dose of study drug (Up to 18.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The APAT population consisted of all participants who received at least one dose of study drug.
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Hide Arm/Group Description:
Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months.
Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months.
Overall Number of Participants Analyzed 641 313
Measure Type: Number
Unit of Measure: Percentage of Participants
1.9 1.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Telcagepant 280 mg/300 mg, Rizatriptan 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-2.0 to 2.0
Estimation Comments Treatment Difference was compared using the MN method.
4.Primary Outcome
Title Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change
Hide Description Predefined limits of change were established for vital sign measurements: Systolic Blood Pressure (>=180 mm Hg and 20 mm Hg increase OR <=90 mm Hg and 20 mm Hg decrease), Diastolic Blood Pressure (>=105 mm Hg and 15 mm Hg increase OR <=50 mm Hg and 15 mm Hg decrease), Pulse (>=120 beats per minute [bpm] and 15 bpm increase OR <=50 bpm and 15 bpm decrease), Body Temperature (>38º C [oral equivalent]) and Respiratory Rate (>25 or increase of 10 OR <5 or decrease of 10 [per minute]). Participants were monitored for vital sign measurements outside predefined limits of change for 14 days after any dose of study drug.
Time Frame Within 14 days of any dose of study drug (Up to 18.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The APAT population consisted of all participants who received at least one dose of study drug.
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Hide Arm/Group Description:
Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months.
Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months.
Overall Number of Participants Analyzed 641 313
Measure Type: Number
Unit of Measure: Percentage of Participants
Systolic Blood Pressure Increase 0.2 0.3
Systolic Blood Pressure Decrease 1.4 1.3
Diastolic Blood Pressure Increase 0.3 0.6
Diastolic Blood Pressure Decrease 1.1 1.0
Pulse Increase 0.0 0.0
Pulse Decrease 0.6 1.6
Body Temperature Increase 0.3 0.3
Respiratory Rate Increase or Decrease 0.8 0.6
5.Secondary Outcome
Title Percentage of Participant Migraine Attacks With Pain Freedom (PF) at 2 Hours Post-Dose
Hide Description Participants were asked to rate their migraine headache severity with ratings of 0=No pain, 1=Mild pain, 2=Moderate pain, and 3=Severe pain. PF at 2 hours post-dose is defined as a decrease from mild, moderate or severe migraine headache (Grade 1, 2, or 3) at baseline to no pain (Grade 0) 2 hours post-dose.
Time Frame 2 hours post-dose (Up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) population consisted of all participants who were randomized and reported at least one treated migraine attack with at least one post-treatment efficacy evaluation.
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Hide Arm/Group Description:
Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months.
Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months.
Overall Number of Participants Analyzed 592 294
Mean (Standard Deviation)
Unit of Measure: Percentage of Migraine Attacks
38.9  (29.5) 47.5  (29.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Telcagepant 280 mg/300 mg, Rizatriptan 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.45 to 0.75
Estimation Comments Based on mixed logistic regression model with a fixed effect term for treatment, baseline pain severity and a random effect term for participant, with the random effect following a normal distribution. An odds ratio >1 is in favor of telcagepant.
Time Frame Up to 14 days after any dose of study drug (Up to 18.5 months)
Adverse Event Reporting Description The population consisted of all participants who received at least one dose of study drug.
 
Arm/Group Title Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Hide Arm/Group Description Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months. Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months.
All-Cause Mortality
Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   12/641 (1.87%)   6/313 (1.92%) 
Ear and labyrinth disorders     
Vertigo  1  1/641 (0.16%)  0/313 (0.00%) 
Eye disorders     
Cataract  1  1/641 (0.16%)  0/313 (0.00%) 
Gastrointestinal disorders     
Nausea  1  1/641 (0.16%)  0/313 (0.00%) 
General disorders     
Non-cardiac chest pain  1  0/641 (0.00%)  1/313 (0.32%) 
Hepatobiliary disorders     
Cholecystitis  1  1/641 (0.16%)  0/313 (0.00%) 
Infections and infestations     
Appendicitis  1  1/641 (0.16%)  0/313 (0.00%) 
Pneumonia  1  1/641 (0.16%)  0/313 (0.00%) 
Injury, poisoning and procedural complications     
Joint injury  1  1/641 (0.16%)  0/313 (0.00%) 
Wrist fracture  1  1/641 (0.16%)  0/313 (0.00%) 
Musculoskeletal and connective tissue disorders     
Chondromalacia  1  1/641 (0.16%)  0/313 (0.00%) 
Patellofemoral pain syndrome  1  1/641 (0.16%)  0/313 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  1/641 (0.16%)  0/313 (0.00%) 
Sqamous cell carcinoma  1  1/641 (0.16%)  0/313 (0.00%) 
Nervous system disorders     
Migraine  1  0/641 (0.00%)  1/313 (0.32%) 
Syncope  1  0/641 (0.00%)  1/313 (0.32%) 
Psychiatric disorders     
Bipolar disorder  1  1/641 (0.16%)  0/313 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  0/641 (0.00%)  1/313 (0.32%) 
Reproductive system and breast disorders     
Uterovaginal prolapse  1  1/641 (0.16%)  0/313 (0.00%) 
Vaginal prolapse  1  0/641 (0.00%)  1/313 (0.32%) 
Vascular disorders     
Haematoma  1  0/641 (0.00%)  1/313 (0.32%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Telcagepant 280 mg/300 mg Rizatriptan 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   187/641 (29.17%)   127/313 (40.58%) 
Gastrointestinal disorders     
Dry mouth  1  62/641 (9.67%)  43/313 (13.74%) 
Nausea  1  58/641 (9.05%)  20/313 (6.39%) 
General disorders     
Asthenia  1  14/641 (2.18%)  16/313 (5.11%) 
Fatigue  1  31/641 (4.84%)  32/313 (10.22%) 
Infections and infestations     
Upper respiratory tract infection  1  17/641 (2.65%)  16/313 (5.11%) 
Nervous system disorders     
Dizziness  1  57/641 (8.89%)  32/313 (10.22%) 
Somnolence  1  59/641 (9.20%)  52/313 (16.61%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00443209     History of Changes
Other Study ID Numbers: 0974-012
MK-0974-012 ( Other Identifier: Merck Protocol Number )
2006_524 ( Other Identifier: Telerx Study Number )
First Submitted: February 28, 2007
First Posted: March 5, 2007
Results First Submitted: July 29, 2014
Results First Posted: August 18, 2014
Last Update Posted: October 17, 2018