Safety and Pharmacokinetics (PK) Study of Single Ascending Doses of CVT-427 (Zolmitriptan Inhalation Powder) In Healthy Adults

A Phase 1 First in Human Open-Label Study of the Safety and Pharmacokinetics of Single Ascending Doses of CVT-427 (Zolmitriptan Inhalation Powder) In Healthy Adults

This study is the first study in humans with CVT-427 (zolmitriptan inhalation powder) and is designed to evaluate the safety, tolerability, and PK of single ascending doses of CVT-427 in adult healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: zolmitriptan; Drug: CVT-427 (zolmitriptan inhalation powder),

Detailed Description

Objectives:

• To evaluate the overall safety and tolerability of single, inhaled doses of CVT-427 (zolmitriptan inhalation powder) in healthy adults, with special emphasis on cardiopulmonary effects.
• To describe the pharmacokinetics (PK) of single, inhaled doses of CVT-427, Zomig® Tablet, and Zomig® Nasal Spray in healthy adults.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Site 001
  • Texas
    • Dallas, Texas, United States, 75247
      • Site 002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult men or women volunteers aged 18 to 65 years, inclusive;
• Triptan-naïve;
• Body mass index (BMI) between 18 to 30 kg/m2;
• Forced expiratory volume in one second (FEV1) greater than 80% of predicted for race, age, sex, and height and FEV1/FVC (forced vital capacity) ratio greater than or equal to 70%;
• No history of asthma;
• Non-smoking for at least 5 years;
• In good general health with no clinically significant abnormalities or recognized cardiovascular risk factors that preclude use of triptans and that would interfere with participation in this study as determined by medical history, physical examination, electrocardiogram, and clinical laboratory test results; and negative tests for drug and alcohol, serology, and for pregnancy for female subjects of childbearing potential.

Exclusion Criteria:

• Subject who is not surgically sterile or female subject who is less than 2 years postmenopausal, and who does not agree to use a highly effective birth control method during the study and up to 3 months after the last dose of investigational product;
• Any cardiovascular risk factor including clinically relevant ECG parameter (e.g., PR interval, QRS deviation) or other clinically significant ECG abnormality;
• History of asthma (including exercise-induced asthma and cold-induced asthma) or chronic obstructive pulmonary disorder (COPD) requiring intermittent or continuous use of any oral or inhaled medication therapy within last 3 years;
• Any flu-like syndrome or other respiratory infections within 4 weeks of CVT-427 administration;
• Unable to tolerate blood draws.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: CVT-427 (zolmitriptan inhalation powder); Periods 1-2: Subjects will receive Zomig oral tablet in Period 1 and Zomig nasal spray in Period 2, 1 hour apart. Periods 3-6: Subjects will receive CVT-427 (dose levels (DL) 1, 2, 3 and 4), administered in ascending order provided that safety and tolerability data are observed to be adequate to allow dose escalation, approximately 24 hours after preceding DL.

Drug: zolmitriptan; Oral Tablet and Nasal Spray; Other Names: Zomig®; Drug: CVT-427 (zolmitriptan inhalation powder),; Capsules containing zolmitriptan; dose levels equivalent to estimated fine particle dose (i.e., lung-delivered) zolmitriptan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events (AEs) including serious AEs		up to 23 days
Pulmonary function	Measured by spirometry using the guideline specified by the Third National Health and Nutrition Examination Survey (NHANES III)	within 90 min prior to dosing and at specified time points up to 24 hours post-dose
Maximum observed plasma drug concentration (Cmax)		within 15 minutes pre-dose and at specified time points up to 24 hours post-dose
Time to maximum observed plasma drug concentration (Tmax)		within 15 minutes pre-dose and at specified time points up to 24 hours post-dose
Area under the concentration time curve (AUC)		within 15 minutes pre-dose and at specified time points up to 24 hours post-dose
Terminal elimination half-life (t½)		within 15 minutes pre-dose and at specified time points up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Acorda Therapeutics

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): April 1, 2016

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (ESTIMATE): November 20, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): June 6, 2016
• Last Update Submitted That Met QC Criteria: June 3, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Migraine attacks
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Protein Synthesis Inhibitors; Oxazolidinones; Zolmitriptan
• Other Study ID Numbers: TRIP-AM-1035