Efficacy and Safety of Acetaminophen, Aspirin and Caffeine With Sumatriptan in the Acute Treatment of Migraine

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01248468
• Collaborator: (none)
• Enrollment: 752
• Locations: 20
• Arms: 3
• Duration (Months): 3.9
• Patients Per Site: 37.6
• Patients Per Site Per Month: 9.5

Study Details

Study Description

Brief Summary

The main purpose of this study is to compare the efficacy and safety of aspirin, acetaminophen and caffeine (AAC) with sumatriptan and placebo in the acute treatment of migraine.

Condition or Disease	Intervention/Treatment	Phase
Pain, Migraine	Drug: Aspirin, acetaminophen and caffeine; Drug: Sumatriptan; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 752 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Parallel-group Single-dose, Placebo-controlled Study Comparing the Efficacy and Safety of Acetaminophen, Aspirin and Caffeine With Sumatriptan in the Acute Treatment of Migraine.
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aspirin, acetaminophen and caffeine AAC: 2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets	Drug: Aspirin, acetaminophen and caffeine; 2 tablets each containing Aspirin (250mg), acetaminophen (250mg) and caffeine (65mg)
Active Comparator: Sumatriptan (100 mg) 1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	Drug: Sumatriptan; 100 mg Sumatriptan
Placebo Comparator: Placebo 1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	Drug: Placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Percent of Subjects Who Are Pain Free at 2 Hours. [2 hours]

   Subjects assessed severity of pain on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of pain=none at 2 hours were considered pain free at 2 hours

Secondary Outcome Measures

1. Percent of Subjects Who Are Free of Nausea at 2 Hours. [2 hours]

   Subjects assessed severity of relevant symptom on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of relevant symptom=none at 2 hours were considered relevant symptom free at 2 hours

2. Percent of Subjects Who Are Free of Phonophobia at 2 Hours. [2 hours]

   Subjects assessed severity of relevant symptom on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of relevant symptom=none at 2 hours were considered relevant symptom free at 2 hours

3. Percent of Subjects Who Are Free of Photophobia at 2 Hours. [2 hours]

   Subjects assessed severity of relevant symptom on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of relevant symptom=none at 2 hours were considered relevant symptom free at 2 hours

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Male or female aged 18 years and over.

2. International Headache Society (IHS) diagnosis of migraine without aura or typical aura with migraine headache.

3. History of experiencing at least 1, but not more than 8, acute migraine attacks monthly during the previous year.

4. History of at least moderate migraine pain intensity, if left untreated.

Exclusion criteria:

1. Headache symptoms which may be due to or aggravated by:

• Recent (within 6 months) head or neck trauma (e.g., whiplash)

• Head or neck pain secondary to an orthopedic abnormality

• Cluster headache

• Specific migraine variants (e.g., basilar-type artery migraine, ophthalmoplegic migraine, hemiplegic migraine, migraine aura without headache)

• Other serious, non-migraine causes of headache (e.g., increased intracranial pressure, intracranial bleeding, meningitis, malignancy)

• Non-serious, non-migraine causes of headache (e.g., cold, flu, hangover)

1. Routine use (≥ 10 days per month, on average) of any medication having the potential to interfere with the pharmacologic effects or evaluation of the study medications (e.g., narcotic and non-narcotic analgesic products (prescription or over-the-counter), ergotamine-containing and ergot-type medication, anxiolytics, hypnotics, sedatives, 5HT-1 agonists, anti-emetics, or prokinetic drugs).

2. History of vomiting during more than 20% of migraine episodes or confined to bedrest for more than 50% of migraine episodes.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Anaheim	California	United States
2		San Francisco	California	United States
3		Clearwater	Florida	United States
4		Deland	Florida	United States
5		Jacksonville	Florida	United States
6		Miami	Florida	United States
7		Pembroke Pines	Florida	United States
8		West Palm Beach	Florida	United States
9		Chicago	Illinois	United States
10		Ann Arbor	Michigan	United States
11		Springfield	Missouri	United States
12		Bronx	New York	United States
13		Rochester	New York	United States
14		Raleigh	North Carolina	United States
15		Cleveland	Ohio	United States
16		Mount Pleasant	South Carolina	United States
17		Nashville	Tennessee	United States
18		San Antonio	Texas	United States
19		Salt Lake City	Utah	United States
20		Seattle	Washington	United States

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Clinical Project Leader, Novartis Consumer Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT01248468
• Other Study ID Numbers: 176-P-401
• First Posted: Nov 25, 2010
• Last Update Posted: Jul 30, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Novartis: Pain, Migraine
• Additional relevant MeSH terms: Migraine Disorders; Aspirin; Acetaminophen; Sumatriptan; Caffeine

Study Results

Participant Flow

Arm/Group Title	Aspirin, Acetaminophen, and Caffeine	Sumatriptan (100 mg)	Placebo
Arm/Group Description	2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets	1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets
Period Title: Overall Study
STARTED	299	304	149
Safety Population	266	271	133
ITT Population	256	261	125
COMPLETED	284	290	145
NOT COMPLETED	15	14	4

Baseline Characteristics

Arm/Group Title	Aspirin, Acetaminophen, and Caffeine	Sumatriptan (100 mg)	Placebo	Total
Arm/Group Description	2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets	1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	Total of all reporting groups
Overall Participants	299	304	149	752
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38 (11.4)	37.8 (11.4)	37.6 (11.5)	37.8 (11.4)
Sex: Female, Male (Count of Participants)
Female	250 83.6%	245 80.6%	125 83.9%	620 82.4%
Male	49 16.4%	59 19.4%	24 16.1%	132 17.6%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	1 0.3%	1 0.3%	0 0%	2 0.3%
Asian	3 1%	9 3%	5 3.4%	17 2.3%
Native Hawaiian or Other Pacific Islander	1 0.3%	2 0.7%	0 0%	3 0.4%
Black or African American	44 14.7%	47 15.5%	24 16.1%	115 15.3%
White	244 81.6%	239 78.6%	113 75.8%	596 79.3%
Other	6 2%	6 2%	7 4.7%	19 2.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	299 100%	304 100%	149 100%	752 100%

Outcome Measures

1. Primary Outcome

Title	Percent of Subjects Who Are Pain Free at 2 Hours.
Description	Subjects assessed severity of pain on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of pain=none at 2 hours were considered pain free at 2 hours
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

The basic population for efficacy analysis was ITT. No explicit process to impute missing values at any given assessment timepoint. Instead, missing values were implicitly imputed by the repeated measures analysis statistical model. So, at any given timepoint, the number of subjects analyzed is slightly less than the total ITT population.

Arm/Group Title	Aspirin, Acetaminophen, and Caffeine	Sumatriptan (100 mg)	Placebo
Arm/Group Description	2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets	1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets
Measure Participants	248	256	121
Number [Percent of participants]	34.7 11.6%	44.9 14.8%	26.4 17.7%

2. Secondary Outcome

Title	Percent of Subjects Who Are Free of Nausea at 2 Hours.
Description	Subjects assessed severity of relevant symptom on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of relevant symptom=none at 2 hours were considered relevant symptom free at 2 hours
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

The basic population for efficacy analysis was ITT. No explicit process to impute missing values at any given assessment timepoint. Missing values were implicitly imputed by the repeated measures analysis statistical model. Consequently, at any given timepoint, the number of subjects analyzed is slightly less than the total ITT population.

Arm/Group Title	Aspirin, Acetaminophen, and Caffeine	Sumatriptan (100 mg)	Placebo
Arm/Group Description	2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets	1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets
Measure Participants	248	252	119
Number [percent of participants]	70.6 23.6%	72.2 23.8%	66.4 44.6%

3. Secondary Outcome

Title	Percent of Subjects Who Are Free of Phonophobia at 2 Hours.
Description	Subjects assessed severity of relevant symptom on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of relevant symptom=none at 2 hours were considered relevant symptom free at 2 hours
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

The basic population for efficacy analysis was ITT. No explicit process to impute missing values at any given assessment timepoint. Missing values were implicitly imputed by the repeated measures analysis statistical model. Consequently, at any given timepoint, the number of subjects analyzed is slightly less than the total ITT population.

Arm/Group Title	Aspirin, Acetaminophen, and Caffeine	Sumatriptan (100 mg)	Placebo
Arm/Group Description	2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets	1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets
Measure Participants	247	256	119
Number [Percent of participants]	53.4 17.9%	60.9 20%	46.2 31%

4. Secondary Outcome

Title	Percent of Subjects Who Are Free of Photophobia at 2 Hours.
Description	Subjects assessed severity of relevant symptom on a 4 point scale (0=none, …, 3=severe) at set time points after dosing through 4 hours. Subjects who indicated severity of relevant symptom=none at 2 hours were considered relevant symptom free at 2 hours
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aspirin, Acetaminophen, and Caffeine	Sumatriptan (100 mg)	Placebo
Arm/Group Description	2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets	1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets	1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets
Measure Participants	247	256	120
Number [Percent of participants]	48.6 16.3%	52.3 17.2%	40.8 27.4%

Adverse Events

Arm/Group Title	Aspirin, Acetaminophen, and Caffeine		Sumatriptan (100 mg)		Placebo
Arm/Group Description	2 tablets, each containing acetaminophen 250 mg, aspiring 250 mg, caffeine 65 mg and 1 placebo tablet matching sumatriptan 100 mg tablets		1 tablet containing sumatriptan 100 mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets		1 placebo tablet matching sumatriptan 100mg and 2 placebo tablets matching acetaminophen 250 mg, aspirin 250 mg and caffeine 65 mg tablets
All Cause Mortality
	Aspirin, Acetaminophen, and Caffeine		Sumatriptan (100 mg)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Aspirin, Acetaminophen, and Caffeine		Sumatriptan (100 mg)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/266 (0%)		0/271 (0%)		0/133 (0%)
Other (Not Including Serious) Adverse Events
	Aspirin, Acetaminophen, and Caffeine		Sumatriptan (100 mg)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/266 (3%)		14/271 (5.2%)		3/133 (2.3%)
Gastrointestinal disorders
Nausea	8/266 (3%)		14/271 (5.2%)		3/133 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Data of &/or resulting from the performance of the Clinical Trial (CT) shall be pooled with the data from other centers & analyzed as stipulated in the Protocol.Without the consent of the steering committee of the multi-center CT, no presentation/publication of the results obtained from datasets other than the final pooled dataset shall be made prior to the presentation/ publication based on the final pooled dataset.