Trial Outcomes & Findings for Pharmacokinetics & Tolerability Study of MAP0004 Co-administered With Ketoconazole (NCT NCT01468558)

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

Target enrollment

24 participants

Primary outcome timeframe

48 hours

Results posted on

2014-01-09

Participant Flow

All subjects received MAP0004 on Day 1 of Visit 2, Ketoconazole on Days 3 through 6 of Visit 2, and MAP0004 again on Day 6 of Visit 2. Subjects then returned for Visit 3, 7-11 days from the end of Visit 2. At Visit 3 subjects received 1.0 mg Intravenous (IV) Dihydroergotamine Mesylate (DHE).

Participant milestones

Participant milestones
Measure	Overall Study Subjects first received MAP0004 1.0mg via oral inhalation followed by 48 hours of PK sampling, they then received Ketoconazole (400mg once a day for 4 days) followed by MAP0004 1.0mg and another 48 hours of PK sampling. After a 7-11 day washout, subjects returned to the clinic to receive 1.0mg IV DHE and 48 hours of PK sampling.
Overall Study STARTED	24
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics & Tolerability Study of MAP0004 Co-administered With Ketoconazole

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=24 Participants All subjects that were enrolled in the study.
Age, Continuous	29.58 years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	8 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 n=21 Participants MAP0004 1.0mg via inhalation on Day 1 of Visit 2.	MAP0004 1.0mg + Ketoconazole n=23 Participants Ketoconazole 400mg once a day on Days 3-6 of Visit 2 and MAP0004 1.0mg via inhalation on Day 6 of Visit 2.	IV DHE 1.0mg n=20 Participants IV DHE 1.0mg on Day 1 of Visit 3.
Cmax of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration	2582.507 pg/ml Standard Deviation 1137.829	2495.100 pg/ml Standard Deviation 1130.850	27771.234 pg/ml Standard Deviation 36191.528

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 n=23 Participants MAP0004 1.0mg via inhalation on Day 1 of Visit 2.	MAP0004 1.0mg + Ketoconazole n=23 Participants Ketoconazole 400mg once a day on Days 3-6 of Visit 2 and MAP0004 1.0mg via inhalation on Day 6 of Visit 2.	IV DHE 1.0mg n=20 Participants IV DHE 1.0mg on Day 1 of Visit 3.
AUC(0-48) of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration	3484.725 pg*h/ml Standard Deviation 1221.423	4070.611 pg*h/ml Standard Deviation 1628.973	9229.171 pg*h/ml Standard Deviation 3130.093

Adverse Events

MAP0004 1.0mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

MAP0004 1.0mg + Ketoconazole

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

IV DHE 1.0mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	MAP0004 1.0mg n=24 participants at risk MAP0004 1.0mg via inhalation on Day 1 of Visit 2.	MAP0004 1.0mg + Ketoconazole n=24 participants at risk Ketoconazole 400mg once a day on Days 3-6 of Visit 2 and MAP0004 1.0mg via inhalation on Day 6 of Visit 2.	IV DHE 1.0mg n=22 participants at risk IV DHE 1.0mg on Day 1 of Visit 3.
Gastrointestinal disorders Diarrhea	4.2% 1/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	9.1% 2/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.
Gastrointestinal disorders Nausea	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	4.2% 1/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	50.0% 11/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.
Gastrointestinal disorders Vomiting	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	13.6% 3/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	18.2% 4/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.
Nervous system disorders Dizziness	4.2% 1/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	4.2% 1/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	18.2% 4/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.
Nervous system disorders Headache	25.0% 6/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	29.2% 7/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	22.7% 5/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.
Skin and subcutaneous tissue disorders Rash	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	8.3% 2/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	0.00% 0/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.
Vascular disorders Hot flush	0.00% 0/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	4.2% 1/24 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.	13.6% 3/22 All 24 subjects who received MAP0004 alone, 24 subjects who received MAP0004 with ketoconazole, and 22 subjects who received IV DHE are included in the adverse event analysis. Adverse events are presented by treatment arm, not necessarily by individual treatment (intervention) received.

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