Trial Outcomes & Findings for Pharmacokinetics & Tolerability Study of MAP0004 in Smoking and Non-Smoking Adult Volunteers (NCT NCT01199965)

NCT ID: NCT01199965

Last Updated: 2014-01-09

Results Overview

The maximum concentration (Cmax) is the highest concentration of a drug measured in the plasma. Plasma is the clear portion of the blood. The Cmax of Dihydroergotamine is reported in picograms per milliliter (pg/ml).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

47 participants

Primary outcome timeframe

48 hours

Results posted on

2014-01-09

Participant Flow

All smoking and non-smoking subjects received both MAP0004 and Intravenous (IV) Dihydroergotamine (DHE).

Participant milestones

Participant milestones
Measure	Smokers Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result.	Non-smokers Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening.
Overall Study STARTED	23	24
Overall Study COMPLETED	22	24
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics & Tolerability Study of MAP0004 in Smoking and Non-Smoking Adult Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Smokers n=23 Participants Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result.	Non-smokers n=24 Participants Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening.	Total n=47 Participants Total of all reporting groups
Age, Continuous	32.91 years STANDARD_DEVIATION 7.1 • n=5 Participants	30.71 years STANDARD_DEVIATION 8.8 • n=7 Participants	31.79 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48 hours

Population: Patients with available data at specified time points are included in the analysis population.

Outcome measures

Outcome measures
Measure	MAP0004 1.0mg Smokers n=22 Participants Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result and receiving MAP0004 at either Visit 2 or 3.	MAP0004 1.0mg Non-smokers n=24 Participants Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening and receiving MAP0004 at either Visit 2 or 3.	IV DHE 1.0mg Smokers n=22 Participants Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result and receiving IV DHE at either Visit 2 or 3.	IV DHE 1.0mg Non-smokers n=24 Participants Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening and receiving IV DHE at either Visit 2 or 3.
Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers	1282.059 pg/ml Standard Deviation 636.138	2550.727 pg/ml Standard Deviation 1297.097	60046.128 pg/ml Standard Deviation 49580.385	48428.635 pg/ml Standard Deviation 43894.253

PRIMARY outcome

Timeframe: 48 hours

Population: Patients with available data at specified time points are included in the analysis population.

The AUC(0-48) is the area under the plot of plasma concentration of drug against time after drug administration. Dihydroergotamine AUC(0-48) is reported in picograms times hour per milliliter (pg\*h/ml).

Outcome measures

Outcome measures
Measure	MAP0004 1.0mg Smokers n=23 Participants Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result and receiving MAP0004 at either Visit 2 or 3.	MAP0004 1.0mg Non-smokers n=24 Participants Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening and receiving MAP0004 at either Visit 2 or 3.	IV DHE 1.0mg Smokers n=22 Participants Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result and receiving IV DHE at either Visit 2 or 3.	IV DHE 1.0mg Non-smokers n=24 Participants Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening and receiving IV DHE at either Visit 2 or 3.
AUC(0-48) of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers and Non-smokers	3014.968 pg*h/ml Standard Deviation 1136.162	4148.750 pg*h/ml Standard Deviation 1533.861	11049.027 pg*h/ml Standard Deviation 3744.094	11731.639 pg*h/ml Standard Deviation 3167.828

Adverse Events

MAP0004 1.0mg Smokers

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

MAP0004 1.0mg Non-smokers

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

IV DHE 1.0mg Smokers

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

IV DHE 1.0mg Non-smokers

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

VP, Scientific Affairs

MAP Pharmaceuticals Inc., a wholly owned subsidiary of Allergan

Phone: 650-386-3100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	MAP0004 1.0mg Smokers n=23 participants at risk Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result and receiving MAP0004 at either Visit 2 or 3.	MAP0004 1.0mg Non-smokers n=24 participants at risk Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening and receiving MAP0004 at either Visit 2 or 3.	IV DHE 1.0mg Smokers n=22 participants at risk Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result and receiving IV DHE at either Visit 2 or 3.	IV DHE 1.0mg Non-smokers n=24 participants at risk Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening and receiving IV DHE at either Visit 2 or 3.
Musculoskeletal and connective tissue disorders Back pain	4.3% 1/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	4.2% 1/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	9.1% 2/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	4.5% 1/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	16.7% 4/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	13.6% 3/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Nervous system disorders Dizziness	4.3% 1/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	4.2% 1/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	27.3% 6/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Nervous system disorders Headache	8.7% 2/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	27.3% 6/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	41.7% 10/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Nervous system disorders Paraesthesia	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	4.5% 1/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Vascular disorders Flushing	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	9.1% 2/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	20.8% 5/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Gastrointestinal disorders Diarrhoea	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	4.5% 1/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Gastrointestinal disorders Nausea	4.3% 1/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	22.7% 5/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	37.5% 9/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Gastrointestinal disorders Vomiting	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	9.1% 2/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	20.8% 5/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
Infections and infestations Rhinitis	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	4.2% 1/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
General disorders Chest discomfort	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	9.1% 2/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	12.5% 3/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
General disorders Fatigue	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	4.2% 1/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	9.1% 2/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.
General disorders Feeling hot	0.00% 0/23 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	0.00% 0/22 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.	8.3% 2/24 All 24 non-smoking subjects who received MAP0004 and IV DHE and 23 smoking subjects who received MAP0004 and 22 of the 23 smoking subjects received IV DHE were included in the adverse event analysis.