Healthy Subjects
Conditions
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.
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.
Interventions
DRUGVaenicline oral tablet 1 mg, then OC-01 (varenicline solution) nasal spray 0.12 mg
Cross over bioavailability study
DRUGOC-01 (varenicline solution) nasal spray 0.12 mg then Varenicline oral tablet 1 mg
Cross over bioavailability study
Sponsors
Oyster Point Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OC-01 (Varenicline Solution) Nasal Spray 0.12 mg Then Varenicline Oral Tablet 1 mg 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. | 11 |
| Varenicline Oral Tablet 1 mg Then OC-01 (Varenicline Solution) Nasal Spray 0.12 mg 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. | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|
| Age, Customized age | 39.5 years STANDARD_DEVIATION 10.6 | 44.5 years STANDARD_DEVIATION 14 | 42.0 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 9 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 13 / 21 | 9 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 |
Outcome results
Primary
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.
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.
Population: Pharmacokinetic analysis set. Subjects who completed both periods and have sufficient data to calculate AUC0-∞
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Oral Tablet 1 mg | AUC0-inf | 8.3 h*ng/mL | Standard Deviation 4.09 |
| OC-01 (Varenicline) Nasal Spray 0.12 mg | AUC0-inf | 102.83 h*ng/mL | Standard Deviation 16.82 |
Primary
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.
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.
Population: Pharmacokinetic analysis set. Subjects who completed both periods and have sufficient data to calculate AUC0-t were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Oral Tablet 1 mg | AUC0-t | 4.49 h*ng/ml | Standard Deviation 3.42 |
| OC-01 (Varenicline) Nasal Spray 0.12 mg | AUC0-t | 98.74 h*ng/ml | Standard Deviation 25.49 |
Primary
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.
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.
Population: Pharmacokinetic analysis set. Subjects who completed both periods and have sufficient data to calculate Cmax were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Oral Tablet 1 mg | Cmax | 0.34 ng/ml | Standard Deviation 0.13 |
| OC-01 (Varenicline) Nasal Spray 0.12 mg | Cmax | 4.63 ng/ml | Standard Deviation 0.93 |
Primary
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.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Varenicline Oral Tablet 1 mg | Tmax | 2.0 h |
| OC-01 (Varenicline) Nasal Spray 0.12 mg | Tmax | 3 h |
Other Pre-specified
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.
Time frame: Baseline to 2 hours post treatment
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Oral Tablet 1 mg | Creatine Shift From Normal at Baseline to Abnormal After 2 Hours Post-treatment | 3 Participants |
| OC-01 (Varenicline) Nasal Spray 0.12 mg | Creatine Shift From Normal at Baseline to Abnormal After 2 Hours Post-treatment | 3 Participants |