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

• Sponsor: Oyster Point Pharma, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04072146
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.7
• Patients Per Site Per Month: 8.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	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	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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)
• Actual Study Start Date: Aug 26, 2019
• Actual Primary Completion Date: Nov 15, 2019
• Actual Study Completion Date: Nov 15, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. AUC0-t [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.]

   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.

2. AUC0-inf [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 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.

3. Cmax [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 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.

4. Tmax [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 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.

Other Outcome Measures

1. Creatine Shift From Normal at Baseline to Abnormal After 2 Hours Post-treatment [Baseline to 2 hours post treatment]

   Creatine shift from baseline to 2 hours post treatment. Elevated creatinine may indicate impaired kidney function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	United States, Miami Florida	Miami	Florida	United States	33136

Sponsors and Collaborators

• Oyster Point Pharma, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jul 13, 2019
• Statistical Analysis Plan - Sep 9, 2019

More Information

Publications

None provided.

• Responsible Party: Oyster Point Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT04072146
• Other Study ID Numbers: OPP-100
• First Posted: Aug 28, 2019
• Last Update Posted: May 23, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pharmaceutical Solutions; Varenicline

Study Results

Participant Flow

Arm/Group Title	Varenicline Oral Tablet 1 mg, Then OC-01 (Varenicline) Nasal 0.12 mg	OC-01 (Varenicline Solution) Nasal Spray 0.12 mg, Then Varenicline Oral Tablet 1 mg
Arm/Group Description	Treatment sequence A: single oral dose of 1 mg varenicline tablet, washout for 14 days, then treatment sequence B intranasal dose of 0.12 mg OC-01 nasal spray.	Treatment sequence B intranasal dose of 0.12 mg OC-01 nasal spray, washout for 14 days, then treatment sequence A: single oral dose of 1 mg varenicline tablet.
Period Title: Overall Study
STARTED	11	11
COMPLETED	11	10
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	OC-01 (Varenicline Solution) Nasal Spray 0.12 mg Then Varenicline Oral Tablet 1 mg	Varenicline Oral Tablet 1 mg Then OC-01 (Varenicline Solution) Nasal Spray 0.12 mg	Total
Arm/Group Description	Treatment sequence A: single oral dose of 1 mg varenicline tablet, washout for 14 days, then treatment sequence B: intranasal dose of 0.12 mg OC-01 nasal spray.	Treatment sequence B: intranasal dose of 0.12 mg OC-01 nasal spray, washout for 14 days, then treatment sequence A: single oral dose of 1 mg varenicline tablet.	Total of all reporting groups
Overall Participants	11	11	22
Age, Customized (years) [Mean (Standard Deviation) ]
age	39.5 (10.6)	44.5 (14.0)	42.0 (12.4)
Sex: Female, Male (Count of Participants)
Female	3 27.3%	7 63.6%	10 45.5%
Male	8 72.7%	4 36.4%	12 54.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 90.9%	9 81.8%	19 86.4%
Not Hispanic or Latino	1 9.1%	2 18.2%	3 13.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	AUC0-t
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set. Subjects who completed both periods and have sufficient data to calculate AUC0-t were included.

Arm/Group Title	Varenicline Oral Tablet 1 mg	OC-01 (Varenicline) Nasal Spray 0.12 mg
Arm/Group Description	OC-01 0.12 mg was administered intranasally 50 ul into each nostril in a fasted state Vaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg	Varenicline oral tablet 1mg was administered orally in a fasted stated with 200 ml water OC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg.
Measure Participants	16	16
Mean (Standard Deviation) [h*ng/ml]	4.49 (3.42)	98.74 (25.49)

2. Primary Outcome

Title	AUC0-inf
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set. Subjects who completed both periods and have sufficient data to calculate AUC0-∞

Arm/Group Title	OC-01 (Varenicline) Nasal Spray 0.12 mg	Varenicline Oral Tablet 1 mg
Arm/Group Description	OC-01 0.12 mg was administered intranasally 50 ul into each nostril in a fasted state Vaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg	Varenicline oral tablet 1mg was administered orally in a fasted stated with 200 ml water OC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg
Measure Participants	16	16
Mean (Standard Deviation) [h*ng/mL]	8.3 (4.09)	102.83 (16.82)

3. Primary Outcome

Title	Cmax
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set. Subjects who completed both periods and have sufficient data to calculate Cmax were included.

Arm/Group Title	OC-01 (Varenicline) Nasal Spray 0.12 mg	Varenicline Oral Tablet 1 mg
Arm/Group Description	OC-01 0.12 mg was administered intranasally 50 ul into each nostril in a fasted state Vaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg	Varenicline oral tablet 1mg was administered orally in a fasted stated with 200 ml water OC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg
Measure Participants	16	16
Mean (Standard Deviation) [ng/ml]	0.34 (0.13)	4.63 (0.93)

4. Primary Outcome

Title	Tmax
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	OC-01 (Varenicline) Nasal Spray 0.12 mg	Varenicline Oral Tablet 1 mg
Arm/Group Description	OC-01 0.12 mg was administered intranasally 50 ul into each nostril in a fasted state Vaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg	Varenicline oral tablet 1mg was administered orally in a fasted stated with 200 ml water OC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg
Measure Participants	16	16
Median (Full Range) [h]	2.0	3

5. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	Varenicline Oral Tablet 1mg, Then OC-01 (Varenicline Solution) Nasal Spray 0.12 mg	OC-01 (Varenicline Solution) Nasal Spray 0.12 mg, Then Varenicline Oral Tablet 1 mg
Arm/Group Description	OC-01 0.12 mg was administered intranasally 50 ul into each nostril in a fasted state Vaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg: Cross over bioavailability study	Varenicline oral tablet 1mg was administered orally in a fasted stated with 200 ml water OC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg: Cross over bioavailability study
Measure Participants	22	21
Count of Participants [Participants]	3 27.3%	3 27.3%

Adverse Events

Time Frame	Adverse Events were collected from the first dose of study drug administration until the final study visit (60 days).
Adverse Event Reporting Description	In the Varenicline Oral Tablet 1 mg, Then OC- 01 (Varenicline) Nasal Spray 0.12 mg arm, 1 subject withdrew after receiving the Varenicline oral tablet and before receiving the OC-01 (varenicline) nasal spray
Arm/Group Title	OC- 01 (Varenicline) Nasal Spray 0.12 mg		Varenicline Oral Tablet 1 mg
Arm/Group Description	OC- 01 (varenicline) nasal spray 0.12 mg		Varenicline oral tablet 1 mg
All Cause Mortality
	OC- 01 (Varenicline) Nasal Spray 0.12 mg		Varenicline Oral Tablet 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/22 (0%)
Serious Adverse Events
	OC- 01 (Varenicline) Nasal Spray 0.12 mg		Varenicline Oral Tablet 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	OC- 01 (Varenicline) Nasal Spray 0.12 mg		Varenicline Oral Tablet 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/21 (61.9%)		9/22 (40.9%)
Gastrointestinal disorders
nausea	0/21 (0%)		5/22 (22.7%)
vomiting	0/21 (0%)		4/22 (18.2%)
Abdominal pain upper	0/21 (0%)		1/22 (4.5%)
Dry mouth	0/21 (0%)		1/22 (4.5%)
General disorders
Chills	0/21 (0%)		1/22 (4.5%)
Feeling cold	0/21 (0%)		1/22 (4.5%)
Injury, poisoning and procedural complications
Scratch	0/21 (0%)		1/22 (4.5%)
Nervous system disorders
somnolence	1/21 (4.8%)		3/22 (13.6%)
Head discomfort	0/21 (0%)		1/22 (4.5%)
Headache	0/21 (0%)		1/22 (4.5%)
Dizziness	1/21 (4.8%)		8/22 (36.4%)
Respiratory, thoracic and mediastinal disorders
Sneezing	7/21 (33.3%)		0/22 (0%)
cough	6/21 (28.6%)		0/22 (0%)
Dry throat	0/21 (0%)		1/22 (4.5%)
Nasal congestion	0/21 (0%)		1/22 (4.5%)
Nasal pruritus	1/21 (4.8%)		0/22 (0%)
Rhinorrhea	1/21 (4.8%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.