QT Intervals Study to Compare the Acute Effects of Orally Inhaled Dihydroergotamine (DHE), Oral Moxifloxacin, and Placebo

A Randomized, Double Blind, Placebo Controlled, Three- Period Crossover Study Comparing the Acute Effects of Orally Inhaled Dihydroergotamine (DHE), Oral Moxifloxacin, and Placebo on QT Intervals in Healthy Adults

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01191723

Enrollment

Registered

2010-08-31

Start date

2010-08-31

Completion date

2010-09-30

Last updated

2014-01-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Healthy Volunteers

Brief summary

Compare the acute effect on the QT interval of MAP0004 (Dihydroergotamine Mesylate delivered by Oral Inhalation) with Moxifloxacin and Placebo.

Interventions

DRUGMAP0004

3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol

DRUGInhaler Placebo

Placebo for Inhaler administered in Treatments A and C

DRUGMoxifloxacin

400mg encapsulated tablet administered in Treatment A as per protocol

DRUGPlacebo Capsule

Placebo for Moxifloxacin administered in Treatment B and Treatment C

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

Inclusion criteria

1. Able to provide a signed, executed written informed consent 2. Healthy non-smoking adult volunteers: Male or Female subjects 18 to 45 years old 3. Female subjects who are practicing adequate contraception (see section 4.4) or who are sterile 4. No known cardiac disease 5. Normal hemoglobin values 6. Normal or not clinically significant 12-lead Electrocardiogram * Heart rate ≥ 40 and ≤ 100 at Visit 1 vital signs assessment (resting) * Subjects with QTcF interval duration \<430 msec for males and \<450 msec for females obtained from the ECG recorder's measurements on the screening ECG taken after at least 5 minutes of quiet rest in supine position 7. Demonstrated ability to properly use the Tempo® Inhaler 8. Subject has not donated blood in the last 56 days

Exclusion criteria

1. Contraindication to dihydroergotamine mesylate (DHE) 2. History of hemiplegic or basilar migraine 3. Family history of long QT syndrome 4. Participation in another investigational trial during the 30 days prior to Visit 1

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in QTcI for MAP0004 3.0mg and Placebo at 30 Minutes	baseline and 30 minutes	The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for subject pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.
Change From Baseline in QTcI for MAP0004 3.0mg, Placebo, and Moxifloxacin at 2 Hours	baseline and 2 hours	The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for subject pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.

Secondary

Measure	Time frame	Description
Change From Baseline in QTcF for MAP0004 3.0mg and Placebo at 30 Minutes	baseline and 30 minutes	The Fridericia corrected QT interval(QTcF) is a measurement of the electrical impulses through the largest part of the heart muscle. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.
Change From Baseline in QTcF for MAP0004 3.0mg, Placebo, and Moxifloxacin at 2 Hours	baseline and 2 hours	The Fridericia corrected QT interval(QTcF) is a measurement of the electrical impulses through the largest part of the heart muscle. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.
Change From Baseline in Heart Rate for MAP0004 3.0mg, Placebo, and Moxifloxacin at 30 Minutes and 2 Hours	baseline, 30 minutes, and 2 hours	The heart rate is a measure of how fast or slow the heart beats (measured in beats per minute). A negative change indicates a decrease in heart rate and a positive change indicates an increase in heart rate.

Countries

United States

Participant flow

Pre-assignment details

This is a 3-treatment, 3-period, 6-sequence crossover study. Each subject received all 3 treatments in a randomly assigned order: treatments A, B, and C, the sequences were ABC, ACB, BAC, BCA, CAB, and CBA.

Participants by arm

Arm	Count
All Subjects All subjects enrolled in the study.	54
Total	54

Baseline characteristics

Characteristic	All Subjects
Age, Continuous	28.0 years STANDARD_DEVIATION 6.79
Sex: Female, Male Female	34 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	2 / 54	26 / 54	8 / 54
serious Total, serious adverse events	0 / 54	0 / 54	0 / 54

Outcome results

Primary

Change From Baseline in QTcI for MAP0004 3.0mg and Placebo at 30 Minutes

The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for subject pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.

Time frame: baseline and 30 minutes