Healthy
Conditions
Keywords
Pharmacokinetics
Brief summary
This study is a multiple ascending dose study to Assess the Safety, Tolerability, and Pharmacokinetics of orally dosed PG 760564 Administered Twice Daily to Healthy Male and Female Volunteers for 14 Days (27 Doses).
Detailed description
This study is a multiple ascending dose study to Assess the Safety, Tolerability, and Pharmacokinetics of orally dosed PG 760564 Administered Twice Daily to Healthy Male and Female Volunteers for 14 Days (27 Doses). The study is a multiple rising dose (MRD) study of active drug vs. placebo.
Interventions
DRUGPlacebo
oral capsule, 2x/day for 14 days
DRUGPG-760564
oral capsule, 50 mg, 2x/day for 14 days
Sponsors
Procter and Gamble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males and surgically sterile or post-menopausal (last menstrual period \> 1 year at the time of enrollment) healthy females, 18-45 years of age, inclusive, at screening; * Who have not used tobacco or nicotine-containing products within the past 3 months; * Willing to abstain from caffeine or xanthine-containing beverages, including coffee and tea, chocolate, alcohol, grapefruit juice, and Seville oranges, from 24 hours before admission and for the duration of the study; * Who have a body mass index (BMI) between 18 and 32 kg/m2.
Exclusion criteria
* History of diabetes, cardiovascular, hepatic, renal, or malabsorptive disease; * History of peptic ulcer disease, hemorrhoids, GI surgery (appendectomy and cholecystectomy are allowed), or GI bleeding; * History of autoimmune disease; * History of immunodeficiency or of unusual susceptibility to infectious diseases; * History of tuberculosis, acquired immunodeficiency syndrome (AIDS), or infection with human immunodeficiency virus (HIV); * Any history of hypersensitivity or clinically significant allergy to any drug; * Personal or family history of prolonged QT syndrome or any cardiac conduction abnormality; * Family history of sudden death; * History of uveitis or inflammatory ocular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14 | 14 days | the area under the plasma concentration-time curve over a dosing interval (τ = 12 hours) on Day 14 of Multiple Dose Oral Administration of PG-760564 Given Every 12 Hours |
| Cmax Over a Dosing Interval (τ = 12 Hours)on Day 14 | 12 hours on Day 14 | Maximum plasma concentration (Cmax) over a dosing interval (τ = 12 hours)on Day 14 |
| Tmax Over a Dosing Interval (τ = 12 Hours) on Day 14 | 12 Hours on Day 14 | the time at which maximum plasma concentration occurred (Tmax) Over a Dosing Interval (τ = 12 Hours) on Day 14 |
| t½,z Over a Dosing Interval (τ = 12 Hours)on Day 14 | over a Dosing Interval (τ = 12 Hours) on Day 14 | t½,z is the terminal exponential half-life; over a Dosing Interval (τ = 12 Hours)on Day 14 |
Countries
United States
Participant flow
Pre-assignment details
Each Subject enrolled in the study, participated in one period only (e.g., subjects did not start in the 50mg dose group, then proceed to subsequent groups)
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo capsule. This study consisted of 4 sequential periods testing rising doses of PG 760564. Each period randomized participants to receive either placebo or a specific dose of PG 760564. Subjects enrolled in a period participated in that period only. | 13 |
| 50 mg PG 760564 50 mg PG 760564 Administered Twice for 14 Days (27 Doses). Subjects enrolled in this period participated in one period only (e.g., subjects did not start in the 50mg dose group, then proceed to subsequent groups) | 8 |
| 100 mg PG 760564 100 mg PG 760564 Administered Twice for 14 Days (27 Doses). Subjects enrolled in this period participated in one period only (e.g., subjects did not start in the 100mg dose group, then proceed to subsequent groups) | 8 |
| 200 mg PG 760564 200 mg PG 760564 Administered Twice for 14 Days (27 Doses). Subjects enrolled in this period participated in one period only (e.g., subjects did not start in the 200mg dose group, then proceed to subsequent groups) | 8 |
| 400 mg PG 760564 400 mg PG 760564 Administered Twice for 14 Days (27 Doses). Subjects enrolled in this period participated in one period only (e.g., subjects did not start in the 400mg dose group, then proceed to subsequent groups) | 8 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1 - 50 mg Dose Group | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
| Period 2 - 100 mg Dose Group | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
| Period 4 - 400 mg Dose Group | Adverse Event | 0 | 0 | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | 50 mg PG 760564 | 100 mg PG 760564 | 200 mg PG 760564 | Placebo | 400 mg PG 760564 | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 13 Participants | 8 Participants | 45 Participants |
| Age Continuous | 35.0 years STANDARD_DEVIATION 5.8 | 29.9 years STANDARD_DEVIATION 7.4 | 36.3 years STANDARD_DEVIATION 6.5 | 34.6 years STANDARD_DEVIATION 7.3 | 36.9 years STANDARD_DEVIATION 5.8 | 34.5 years STANDARD_DEVIATION 6.8 |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 13 participants | 8 participants | 45 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 12 Participants | 7 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 13 | 7 / 8 | 7 / 8 | 8 / 8 | 8 / 8 |
| serious Total, serious adverse events | 0 / 13 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14
the area under the plasma concentration-time curve over a dosing interval (τ = 12 hours) on Day 14 of Multiple Dose Oral Administration of PG-760564 Given Every 12 Hours
Time frame: 14 days
Population: PG 760564 blood plasma concentrations were not measured for the placebo arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 mg PG 760564 | AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14 | 12090.998 ng*h/mL | Standard Deviation 2926.95 |
| 100 mg PG 760564 | AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14 | 23472.1329 ng*h/mL | Standard Deviation 9858.248 |
| 200 mg PG 760564 | AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14 | 30005.781 ng*h/mL | Standard Deviation 9955.931 |
| 400 mg PG 760564 | AUCτ Over a Dosing Interval (τ = 12 Hours) on Day 14 | 50354.938 ng*h/mL | Standard Deviation 9781.333 |
Primary
Cmax Over a Dosing Interval (τ = 12 Hours)on Day 14
Maximum plasma concentration (Cmax) over a dosing interval (τ = 12 hours)on Day 14
Time frame: 12 hours on Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 mg PG 760564 | Cmax Over a Dosing Interval (τ = 12 Hours)on Day 14 | 1601.4 ng/mL | Standard Deviation 318.2 |
| 100 mg PG 760564 | Cmax Over a Dosing Interval (τ = 12 Hours)on Day 14 | 2951.3 ng/mL | Standard Deviation 1148.2 |
| 200 mg PG 760564 | Cmax Over a Dosing Interval (τ = 12 Hours)on Day 14 | 3935.0 ng/mL | Standard Deviation 953.1 |
| 400 mg PG 760564 | Cmax Over a Dosing Interval (τ = 12 Hours)on Day 14 | 7195.0 ng/mL | Standard Deviation 279.2 |
Primary
t½,z Over a Dosing Interval (τ = 12 Hours)on Day 14
t½,z is the terminal exponential half-life; over a Dosing Interval (τ = 12 Hours)on Day 14
Time frame: over a Dosing Interval (τ = 12 Hours) on Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 mg PG 760564 | t½,z Over a Dosing Interval (τ = 12 Hours)on Day 14 | 9.411 hours | Standard Deviation 2.64 |
| 100 mg PG 760564 | t½,z Over a Dosing Interval (τ = 12 Hours)on Day 14 | 7.882 hours | Standard Deviation 1.814 |
| 200 mg PG 760564 | t½,z Over a Dosing Interval (τ = 12 Hours)on Day 14 | 10.223 hours | Standard Deviation 3.947 |
| 400 mg PG 760564 | t½,z Over a Dosing Interval (τ = 12 Hours)on Day 14 | 9.701 hours | Standard Deviation 1.714 |
Primary
Tmax Over a Dosing Interval (τ = 12 Hours) on Day 14
the time at which maximum plasma concentration occurred (Tmax) Over a Dosing Interval (τ = 12 Hours) on Day 14
Time frame: 12 Hours on Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 50 mg PG 760564 | Tmax Over a Dosing Interval (τ = 12 Hours) on Day 14 | 2.46 hours | Standard Deviation 0.98 |
| 100 mg PG 760564 | Tmax Over a Dosing Interval (τ = 12 Hours) on Day 14 | 2.89 hours | Standard Deviation 0.63 |
| 200 mg PG 760564 | Tmax Over a Dosing Interval (τ = 12 Hours) on Day 14 | 3.01 hours | Standard Deviation 0.54 |
| 400 mg PG 760564 | Tmax Over a Dosing Interval (τ = 12 Hours) on Day 14 | 2.03 hours | Standard Deviation 0.82 |