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

NCT01191723 | Completed Phase 1 Results

• 1 other identifier: MAP0004-CL-P103
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• 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.

  baseline and 30 minutes

• Change From Baseline in QTcI for MAP0004 3.0mg, Placebo, and Moxifloxacin at 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.

  baseline and 2 hours

Secondary Outcomes (3)

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

  baseline and 30 minutes

• Change From Baseline in QTcF for MAP0004 3.0mg, Placebo, and Moxifloxacin at 2 Hours

  baseline and 2 hours

• 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

Study Arms (6)

Treatment A, then Treatment B, then Treatment C

OTHER

There was 48 hour wash-out between treatment visits. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 2. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 3. Treatment C = inhaler placebo and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.

Drug: MAP0004; Drug: Inhaler Placebo; Drug: Moxifloxacin; Drug: Placebo Capsule

Treatment A, then Treatment C, then Treatment B

OTHER

There was 48 hour wash-out between treatment visits. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 2. Treatment C = inhaler placebo and placebo capsules at Visit 3. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.

Drug: MAP0004; Drug: Inhaler Placebo; Drug: Moxifloxacin; Drug: Placebo Capsule

Treatment B, then Treatment A, then Treatment C

OTHER

There was 48 hour wash-out between treatment visits. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 2. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 3. Treatment C = inhaler placebo and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.

Drug: MAP0004; Drug: Inhaler Placebo; Drug: Moxifloxacin; Drug: Placebo Capsule

Treatment B, then Treatment C, then Treatment A

OTHER

There was 48 hour wash-out between treatment visits. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 2. Treatment C = inhaler placebo and placebo capsules at Visit 3. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 4. Tablets were orally administered after oral inhalation dosing.

Drug: MAP0004; Drug: Inhaler Placebo; Drug: Moxifloxacin; Drug: Placebo Capsule

Treatment C, then Treatment A, then Treatment B

OTHER

There was 48 hour wash-out between treatment visits. Treatment C = inhaler placebo and placebo capsules at Visit 2. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 3. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.

Drug: MAP0004; Drug: Inhaler Placebo; Drug: Moxifloxacin; Drug: Placebo Capsule

Treatment C, then Treatment B, then Treatment A

OTHER

There was 48 hour wash-out between treatment visits. Treatment C = inhaler placebo and placebo capsules at Visit 2. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 3. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 4. Tablets were orally administered after oral inhalation dosing.

Drug: MAP0004; Drug: Inhaler Placebo; Drug: Moxifloxacin; Drug: Placebo Capsule

Interventions

MAP0004 DRUG

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

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

Inhaler Placebo DRUG

Placebo for Inhaler administered in Treatments A and C

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

Moxifloxacin DRUG

400mg encapsulated tablet administered in Treatment A as per protocol

Also known as: Avelox®

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

Placebo Capsule DRUG

Placebo for Moxifloxacin administered in Treatment B and Treatment C

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to provide a signed, executed written informed consent
• Healthy non-smoking adult volunteers: Male or Female subjects 18 to 45 years old
• Female subjects who are practicing adequate contraception (see section 4.4) or who are sterile
• No known cardiac disease
• Normal hemoglobin values
• 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
• Demonstrated ability to properly use the Tempo® Inhaler
• Subject has not donated blood in the last 56 days

You may not qualify if:

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

Sponsors & Collaborators

• Allergan: lead
• MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan: collaborator

Study Sites (1)

Cetero Research

Fargo, North Dakota, United States

Location

Related Publications (1)

• Kori S, Kellerman DJ, Voloshko P, Haugen G. Effects of a supratherapeutic dose of investigational orally inhaled dihydroergotamine (MAP0004) on QT interval: a randomized, double-blind, active- and placebo-controlled crossover study in healthy volunteers. Clin Ther. 2012 Sep;34(9):1920-8. doi: 10.1016/j.clinthera.2012.08.001. Epub 2012 Aug 21.

  PMID: 22917853 DERIVED

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: VP, Scientific Affairs
• Organization: MAP Pharmaceuticals Inc., a wholly owned subsidiary of Allergan

dkellerman@mappharma.com

650-386-3100

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2010
• First Posted: August 31, 2010
• Study Start: August 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: January 9, 2014
• Results First Posted: October 22, 2013

Record last verified: 2013-12

Locations

US (1)