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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Healthy Subjects

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline oral tablet 1mg, then OC-01 (varenicline solution) nasal spray 0.12 mg<br>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<br>* Cross over bioavailability study<br>* Other names: varenicline;|
| Active Comparator: OC-01 (varenicline solution) nasal spray 0.12 mg, then Varenicline oral tablet 1 mg<br>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<br>* Cross over bioavailability study<br>* Other names: varenicline;|

What is the study measuring?
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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. |