Pharmacokinetic Study Evaluating Staccato® Alprazolam 1 mg Inhaler in Smokers Versus Non-Smokers

A Phase 1 Open-Label, Non-Randomized, Single-Dose, Pharmacokinetic Study Evaluating Staccato® Alprazolam 1 mg Inhaler in Smoker Versus Non-Smoker Healthy Adult Volunteers

This is an open-label, non-randomized, single dose, pharmacokinetic study in 36 healthy adult male and female volunteers, including 18 smokers and 18 non-smokers. All subjects will be administered a single inhaled dose of Staccato alprazolam 1 mg via hand-held inhaler. Blood samples will be drawn for pharmacokinetic analysis. Eligible subjects are admitted to Phase 1 unit for up to 48 hours. Subjects will receive a post-study safety phone call 14 days(± 2 days) after dosing.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Staccato Alprazolam 1 mg

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Clinilabs Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• These inclusion criteria (items 1-8) apply to all subjects, smokers and non-smokers:

I. Healthy male and female subjects between the ages of21 to 50 years, inclusive.

2. Body mass index (BMI) >/= 18 and </= 30 kg/m2, inclusive.

3. Able to speak, read, and understand English and are willing and able to provide written informed consent on an IRB-approved form prior to the initiation of any study procedures.

4. Willing and able to be confined to a clinical research facility for up to 48 hours (including 2 nights) and comply with the study schedule and study requirements.

5. Normal spirometry at screening as demonstrated by FEVI +/- 80% of predicted and FVC +/- 80% of predicted.

6. Adequate veins, as assessed by the Investigator or Investigator's designee, that are suitable for the required number and frequency of PK blood draws in this study.

7. In otherwise good general health as determined by a complete medical history, physical examination, 12-lead electrocardiogram (ECG), blood chemistry profile, hematology, serology (HIV-l/2Ab, HBsAg, HCV Ab), and urinalysis at screening.

8. Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method throughout the study and for one week following the end of the study.

Smokers must meet the following inclusion criteria (items 9-10):

9. A history of smoking> 15 cigarettes/day currently and for at least the last 2 years.

10. Serum cotinine +/-500 ng/mL at Screening Visit I.

Nonsmokers must meet the following inclusion criteria (items 11-12):

11. A history of never smoking> 5 cigarettes/day and not smoking at all for at least the last 2 years prior to Visit I.

12. Serum cotinine :o 40 ng/mL at Screening Visit I and a negative urine cotinine test at Visit 2 Day-I.

Exclusion Criteria:

1. Treatment with an investigational drug within 30 days ( or within 5 half-lives of the investigational drug, if>30 days) prior to Visit I.
2. Significant hepatic, renal, gastroenterologic, cardiovascular endocrine, neurologic (including history of seizures or stroke), or hematologic disease.
3. Any acute illness in the 5 days prior to Visit 2.
4. Upper respiratory tract infection within 6 weeks of Visit 2 or bronchitis or pneumonia within 6 months of Visit 2.
5. Use of a bronchodilator for the treatment of wheezing within 12 months of Visit I.
6. Diagnosis of an active or chronic pulmonary disease.
7. Lung resection or other pulmonary surgery within 12 months of Visit I.
8. A history of allergy or intolerance to alprazolam.
9. Use of any other prescription or nonprescription medication--with the exception of acetaminophen, ibuprofen or ongoing doses of oral contraceptives or vitamins--within 5 days prior to study drug administration.
10. A history within the past 2 years of drug or alcohol dependence or abuse.
11. Positive test for alcohol or a positive urine screen for drugs of abuse at screening
12. A positive HIV test.
13. Breastfeeding or a positive pregnancy test at screening (female subjects).
14. Clinically significant ECG abnormality.
15. Hypotension or hypertension, at screening or baseline.
16. Poor veins in the opinion of the Investigator or the Investigator's designee such that the participant is judged to likely have difficult venipuncture during the study.
17. Any other disease or condition, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results.
18. Participation in another clinical trial within 2 months of the beginning of the present study, or blood donation or comparable blood loss (>350mL) within 2 months before the present study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Staccato Alprazolam 1 mg; a single inhaled dose	Drug: Staccato Alprazolam 1 mg; alprazolam I mg administered via the Staccato hand-held inhaler device system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) : Maximum observer drug concentration (Cmax)	Cmax of alprazolam in smokers compared to non-smokers	Sequential time points : pre-dose, and at 2, 5, 10 and 30 minutes, and at 1, 2, 4, 6, 12, 24 and 36 hours post-dose.
PK: Area under the concentration versus time curve (AUC)from Zero to Infinity (AUC[0-∞]	AUC[0-∞] of alprazolam in smokers compared to non-smokers	Sequential time points : pre-dose, and at 2, 5, 10 and 30 minutes, and at 1, 2, 4, 6, 12, 24 and 36 hours post-dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK;: time after administration of a drug when the maximum plasma concentration is reached (Tmax)	Tmax of alprazolam in smokers compared to non-smokers	Sequential time points : pre-dose, and at 2, 5, 10 and 30 minutes, and at 1, 2, 4, 6, 12, 24 and 36 hours post-dose.
PK: half-life (t1/2)	t1/2 of alprazolam in smokers compared to non-smokers	Sequential time points : pre-dose, and at 2, 5, 10 and 30 minutes, and at 1, 2, 4, 6, 12, 24 and 36 hours post-dose.

Collaborators and Investigators

• Sponsor: Engage Therapeutics, Inc.
• Collaborators: Clinilabs, Inc.
• Investigators: Principal Investigator: M. Shenouda, MD, Clinilabs, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2018
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: April 24, 2018
• First Submitted That Met QC Criteria: April 24, 2018
• First Posted (Actual): May 4, 2018

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Alprazolam
• Other Study ID Numbers: EPK-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No