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Phase 3 Study of MAP0004 in Adult Migraineurs (FREEDOM301)

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: NCT00623636
Recruitment Status : Completed
First Posted : February 26, 2008
Results First Posted : October 29, 2013
Last Update Posted : January 9, 2014
Sponsor:
Collaborator:
MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
Information provided by (Responsible Party):
Allergan

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Migraine Disorders
Interventions Drug: MAP0004
Drug: Placebo
Enrollment 902
Recruitment Details  
Pre-assignment Details This study included a Double-blind period for 8 weeks followed by an open-label period that lasted an additional 52 weeks. All patients participating in the open-label period received MAP0004.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks. MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Period Title: Double Blind
Started 452 450
Completed 419 422
Not Completed 33 28
Period Title: Open Label
Started 0 [1] 675 [2]
Completed 0 263
Not Completed 0 412
[1]
Eligible double-blind placebo patients received MAP0004 in the open-label period.
[2]
Includes eligible Placebo and MAP0004 patients from the double-blind period.
Arm/Group Title Placebo MAP0004 Total
Hide Arm/Group Description Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks. MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 397 397 794
Hide Baseline Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 397 participants 397 participants 794 participants
39.6  (11.67) 40.5  (11.30) 40.1  (11.49)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 397 participants 397 participants 794 participants
Female
362
  91.2%
365
  91.9%
727
  91.6%
Male
35
   8.8%
32
   8.1%
67
   8.4%
1.Primary Outcome
Title Number of Subjects With Pain Relief at 2 Hours From Time of First Dose
Hide Description

Pain relief at 2 hours was defined as change in rating from severe or moderate (score 3 or 2) to a rating of none or mild (score 0 or 1) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours.

The 4-point scale from the International Headache Society was used:

0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame 2 hours from time of first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
136 231
2.Primary Outcome
Title Number of Subjects Photophobia Free at 2 Hours From Time of First Dose
Hide Description

Photophobia free at 2 hours was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours.

The 4-point scale from the International Headache Society was used:

0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame 2 hours from time of first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
107 182
3.Primary Outcome
Title Number of Subjects Phonophobia Free at 2 Hours From Time of First Dose
Hide Description

Phonophobia free at 2 hours was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours.

The 4-point scale from the International Headache Society was used:

0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame 2 hours from time of first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
133 208
4.Primary Outcome
Title Number of Subjects Nausea Free at 2 Hours From Time of First Dose
Hide Description

Nausea free was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours post-dose.

The 4-point scale from the International Headache Society was used:

0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame 2 hours from time of first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
234 266
5.Secondary Outcome
Title Number of Subjects With Sustained Pain Relief From 2 to 24 Hours
Hide Description

Sustained Pain Relief was defined as a rating of none or mild (score 0 or 1) at the 2-hour time point that was maintained during the 2-24 hour post-dose period and no use of rescue medication from the time of first dose to 24 hours.

The 4-point scale from the International Headache Society was used:

0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame From 2 to 24 hours from time of first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
76 166
6.Secondary Outcome
Title Number of Subjects Whose Time to Pain Relief Occurred Within 2 Hours
Hide Description

The number of subjects who reported pain relief (score of 0 or 1) at any time within the 2 hours following the time of first dose and who did not use rescue medication on or prior to this point. Subjects who did not reach pain relief by the end of the time period were not included.

The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame 2 hours from the first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
156 244
7.Secondary Outcome
Title Number of Subjects With Pain Relief at 4 Hours
Hide Description

Pain Relief at 4 hours was defined as a change in rating from severe or moderate (score 3 or 2) to none or mild (score 0 or 1) at the 4-hour time point and no use of rescue medication from the time of first dose to 4 hours.

The 4-point scale from the International Headache Society was used:

0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame 4 hours from time of first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
145 254
8.Secondary Outcome
Title Number of Subjects With Pain Relief at 10 Minutes
Hide Description

Pain Relief at 10 minutes was defined as a change in rating from severe or moderate (score 3 or 2) to none or mild (score 0 or 1) at the 10 minute time point and no use of rescue medication from the time of first dose to 2 hours.

The 4-point scale from the International Headache Society was used:

0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities

Time Frame 2 hours from time of first dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
Arm/Group Title Placebo MAP0004
Hide Arm/Group Description:
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks.
Overall Number of Participants Analyzed 397 397
Measure Type: Number
Unit of Measure: participants
30 37
Time Frame [Not Specified]
Adverse Event Reporting Description All subjects who received any dose of study treatment in the double-blind or open-label study period and had at least one post-dose safety evaluation were included in the adverse events analysis.
 
Arm/Group Title Double-blind Placebo Double-blind MAP0004 Open-label MAP0004
Hide Arm/Group Description Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks. MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks. MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks.
All-Cause Mortality
Double-blind Placebo Double-blind MAP0004 Open-label MAP0004
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Double-blind Placebo Double-blind MAP0004 Open-label MAP0004
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/404 (0.00%)   0/410 (0.00%)   14/638 (2.19%) 
Blood and lymphatic system disorders       
Aplastic anemia  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Cardiac disorders       
Acute myocardial infarction  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Gastrointestinal disorders       
Inguinal hernia  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Rectal haemorrhage  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Umbilical hernia  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Infections and infestations       
Gastroenteritis  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Appendicitis  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Septic shock  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Injury, poisoning and procedural complications       
Decompression sickness  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Testicular injury  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Metabolism and nutrition disorders       
Hypokalaemia  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer female  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Nervous system disorders       
Encephalopathy  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Pregnancy, puerperium and perinatal conditions       
Pregnancy  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Psychiatric disorders       
Suicide attempt  1  0/404 (0.00%)  0/410 (0.00%)  2/638 (0.31%) 
Renal and urinary disorders       
Nephrolithiasis  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Reproductive system and breast disorders       
Menorrhagia  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Uterine haemorrhage  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Respiratory, thoracic and mediastinal disorders       
Pleural effusion  1  0/404 (0.00%)  0/410 (0.00%)  1/638 (0.16%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Double-blind Placebo Double-blind MAP0004 Open-label MAP0004
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   60/404 (14.85%)   86/410 (20.98%)   454/638 (71.16%) 
Gastrointestinal disorders       
Nausea  1  7/404 (1.73%)  18/410 (4.39%)  78/638 (12.23%) 
Vomiting  1  3/404 (0.74%)  8/410 (1.95%)  33/638 (5.17%) 
Infections and infestations       
Upper Respiratory Tract Infection  1  12/404 (2.97%)  11/410 (2.68%)  93/638 (14.58%) 
Sinusitis  1  5/404 (1.24%)  3/410 (0.73%)  65/638 (10.19%) 
Nasopharyngitis  1  15/404 (3.71%)  8/410 (1.95%)  67/638 (10.50%) 
Influenza  1  0/404 (0.00%)  3/410 (0.73%)  35/638 (5.49%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  7/404 (1.73%)  10/410 (2.44%)  32/638 (5.02%) 
Social circumstances       
Pharmaceutical Product Compaint  1 [1]  11/404 (2.72%)  25/410 (6.10%)  51/638 (7.99%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
[1]
Medication Aftertaste
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.
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: VP, Scientific Affairs
Organization: MAP Pharmaceuticals Inc., a wholly owned subsidiary of Allergan
Phone: 650-386-3100
EMail: dkellerman@mappharma.com
Layout table for additonal information
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT00623636    
Other Study ID Numbers: MAP0004 CL P301
First Submitted: February 7, 2008
First Posted: February 26, 2008
Results First Submitted: August 19, 2013
Results First Posted: October 29, 2013
Last Update Posted: January 9, 2014