Evaluating Relative Bioavailability of OC-01 (Varenicline) Nasal Spray as Compared to Orally Administered Varenicline

Open-Label, Single-Center, Randomized, 2-way Crossover Study Evaluating Relative Bioavailability of OC-01 (Varenicline) Nasal Spray as Compared to Orally Administered Varenicline (the Zen Study)

To assess the relative bioavailability of varenicline administered intranasally at its highest intended clinical strength compared to varenicline administered orally at its highest oral tablet strength.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Vaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg; Drug: OC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg

Detailed Description

This study was a Phase 1, open-label, randomized, 2-way crossover study to evaluate the relative bioavailability of OC-01 (varenicline) Nasal Spray compared to varenicline administered orally as varenicline oral tablet. Approximately 22 healthy volunteer subjects between 18-65 years of age meeting all other study eligibility criteria were randomized (Treatment Period 1) to receive an intranasal dose of 0.12 mg OC-01 (50 µL spray of 0.06 mg into each nostril) or a single 1 mg oral dose of varenicline oral tablet. Both administrations were delivered while subject is in an overnight fasted state. Subjects then returned at least 14 days later (Treatment Period 2) to receive the alternate dose of varenicline that was delivered at Treatment Period 1. Again, this delivery was performed while subject was in an overnight fasted state.

Participants who terminated early during the application period were asked to complete safety assessments (if the participants agree) prior to study exit. Participants who were terminated early from the study were not replaced.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • United States, Miami Florida

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:

• Body mass index between 18.0 and 32.0 kg/m2, inclusive.
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, ECG and laboratory tests.
• Have provided verbal and written informed consent
• If a female of childbearing potential who is not using an acceptable means of birth control (acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives, mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom, IUD, or surgical sterilization of partner), have a negative urine pregnancy test at the Screening Visit.

Exclusion Criteria:

• Have had nasal or sinus surgery (including history of application of nasal cautery) or significant trauma to these areas.
• Have a vascularized polyp, severely deviated septum, chronic recurrent nosebleeds, or severe nasal airway obstruction as confirmed by intranasal examination at the Screening Visit.
• Any contraindication to varenicline according to the applicable label.
• Have severe renal impairment (estimated creatinine clearance less than 30mL per minute)
• Have current concomitant use of snuff, chewing tobacco, e-cigarettes or cigarettes/cigars during the study
• Have any condition or history that, in the opinion of the investigator, may interfere with study compliance, outcome measures, safety parameters, and/or the general medical condition of the subject
• Be a female who is pregnant, nursing an infant, or planning a pregnancy at the Screening Visit. Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom; IUD; or surgical sterilization of partner.
• Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days prior to the Screening Visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Varenicline oral tablet 1mg, then OC-01 (varenicline solution) nasal spray 0.12 mg; OC-01 0.12 mg was administered intranasally 50 ul into each nostril in a fasted state	Drug: Vaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg; Cross over bioavailability study; Other Names: varenicline
Active Comparator: OC-01 (varenicline solution) nasal spray 0.12 mg, then Varenicline oral tablet 1 mg; Varenicline oral tablet 1mg was administered orally in a fasted stated with 200 ml water	Drug: OC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg; Cross over bioavailability study; Other Names: varenicline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t	Area under the curve from predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.	Blood samples were taken predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.
AUC0-inf	AUC0-inf taken at predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.	Blood samples were taken predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.
Cmax	Cmax taken at predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.	Blood samples were taken predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.
Tmax	Tmax taken at predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.	Blood samples were taken predose (time 0), 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post dose.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Creatine Shift From Normal at Baseline to Abnormal After 2 Hours Post-treatment	Creatine shift from baseline to 2 hours post treatment. Elevated creatinine may indicate impaired kidney function.	Baseline to 2 hours post treatment

Collaborators and Investigators

• Sponsor: Oyster Point Pharma, Inc.
• Investigators: Study Director: Jeffrey Nau, PhD, Oyster Point Pharma, Inc.

Publications and helpful links

General Publications

• Nau J, Wyatt DJ, Rollema H, Crean CS. A Phase I, Open-label, Randomized, 2-Way Crossover Study to Evaluate the Relative Bioavailability of Intranasal and Oral Varenicline. Clin Ther. 2021 Sep;43(9):1595-1607. doi: 10.1016/j.clinthera.2021.07.020. Epub 2021 Aug 27.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2019
• Primary Completion (Actual): November 15, 2019
• Study Completion (Actual): November 15, 2019

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Pharmaceutical Solutions; Varenicline
• Other Study ID Numbers: OPP-100

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