A Phase 1, First in Human, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose and Open Label Food Effect Study to Evaluate Safety, Tolerability, and Pharmacokinetics of OR-101 Administered Orally in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- OR-101 (Single ascending dose)
- Conditions
- Alopecia Areata
- Sponsor
- Ornovi, Inc.
- Locations
- 1
- Primary Endpoint
- Number of participants with Treatment emergent Adverse events (TEAEs)
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
Brief Summary
This first in human phase 1 study to Study will evaluate safety, tolerability, and pharmacokinetics of Single Ascending dose (SAD), Food effect (FE) and Multiple ascending dose (MAD) of OR-101 Administered Orally in healthy subjects
Detailed Description
There are three phases of the study: Single ascending dose (SAD), food effect (FE), and multiple ascending dose (MAD) phases. In the SAD and MAD Phases, up to 64 subjects in each phase may be enrolled in the study. Fortyeight subjects will be randomised in the initial six cohorts; upto 16 subjects may be enrolled in two additional cohorts. For each dose cohort a total of 8 subjects (6 receiving OR-101 and 2 placebo) will be enrolled and randomized. In the FE phase, up to 8 subjects who will receive a high fat meal prior to administration of OR101 may be enrolled in the study. Subjects who discontinue prior to completion may be replaced at the discretion of the Sponsor and the Investigator. The SRC including the Investigator, Medical Monitor, Study Director as well as other ad hoc representatives as appropriate will regularly monitor all aspects of subject safety throughout this study. The SRC will review all available, cumulative safety and PK data in a blinded manner to assess the safety of each dose level of OR-101 prior to escalating to the next dose level.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is willing to sign and date IRB-approved ICF.
- •Is a man or woman between the ages of 18 and 55, inclusive.
- •Has a BMI of 18.0 to 30.5 kg/m2 and a total body weight \>50 kg for a man and \>45 kg for a woman at Screening and Check-in of Day -
- •Is in good health as determined by medical history, PE, clinical laboratory studies, ECGs, VS, and Investigator's judgement (repeat tests are allowed at PI's discretion).
- •Is willing to minimize sun exposure, avoid phototherapy, and not to use tanning beds, tanning booths, or sun lamps during the study (Day 1 to EOS).
- •If a woman of childbearing potential, must not be pregnant, lactating, or planning to become pregnant during the study.
- •Willing to follow the methods of contraception as per the protocol.
Exclusion Criteria
- •Has any condition that precludes a subject's ability to comply with study requirements, including completion of the study visits.
- •Has a history or current evidence of a clinically significant cardiovascular, respiratory, endocrine, gastrointestinal, renal, hepatic, hematologic, immunologic, genitourinary, dermatological, psychiatric or neurologic abnormality or disease or other medical disorder, including cancer or malignancies.
- •Has clinically significant abnormal laboratory test values as determined by the Investigator or the local or Sponsor Medical Monitor.
- •has BP and HR measurement after 5 minutes rest in a supine position of:
- •systolic BP \>150 or \<90 mmHg
- •diastolic BP of \>95 or \<45 mmHg
- •HR \>100 or \<50 bpm
- •2 repeats of the subject's BP or HR are permitted for eligibility purposes
- •Has a history of, or currently has, any clinically significant ECG finding, or a QT interval corrected by Fridericia's method (QTcF) of \> 450 msec for males and \> 470 msec for females.
- •Has unacceptable COVID-19 test results (if required per site policy at the time of enrollment).
Arms & Interventions
Part A
Drug- OR-101 Dosage level: SAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 150mg, 450mg, 900mg, 1500mg OR-101 in dose escalating manner in cohorts 1-6. Dosage form: Solution Route of administration- Oral
Intervention: OR-101 (Single ascending dose)
Part B
Drug- OR101 Dosage level: Food effect participants (8 subjects in 9 cohorts) will only receive OR-101with a high fat meal prior to administration and subjects in corresponding dose under fasted condition will serve as their reference group. Dosage form: Solution Route of administration- Oral
Intervention: OR-101 (Food effect)
Part C
Drug- OR-101 Dosage level: MAD participants will receive either placebo or one of planned doses levels of 15mg, 45mg, 135mg, 270mg, 540mg and 900mg OR-101 in dose escalating manner in cohorts 1-6. Total dosage of cohort 7 and 8 will be decided based on Safety review committe's input where cohort 8 will receive this daily for 7 days. Dosage form: Solution Route of administration- Oral
Intervention: OR-101 (Multiple ascending dose)
Placebo
Placebo comparators taken by participants randomised to the placebo arm across Part A and C of the study.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants with Treatment emergent Adverse events (TEAEs)
Time Frame: Upto 8 days in SAD and FE Phase; Upto 14 days in MAD Phase
Number of participants with Serious Adverse events (SAEs)
Time Frame: Upto 8 days in SAD and FE Phase; Upto 14 days in MAD Phase
Number of participants with changes in 12-lead ECG findings
Time Frame: Upto 8 days in SAD and FE Phase; Upto 14 days in MAD Phase
Number of participants in clinical laboratory tests
Time Frame: Upto 8 days in SAD and FE Phase; Upto 14 days in MAD Phase
Secondary Outcomes
- PK Parameters: Maximum Concentration (Cmax)(SAD and FE- Day1, Day2, Day 3, Day 4 and day 8 post dose; MAD- Day 1 to Day 14 post dose)
- Urine PK Parameters: nonrenal Clearance (CLnr)(SAD Phase only: Urine PK samples at predose void on Day 1, and at 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-60, 60-72 hours postdose.)
- Urine PK Parameters: Renal Clearance (CLr)(SAD Phase only: Urine PK samples at predose void on Day 1, and at 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-60, 60-72 hours postdose.)
- PK Parameters: Tmax(SAD and FE- Day1, Day2, Day 3, Day 4 and day 8 post dose; MAD- Day 1 to Day 14 post dose)
- PK Parameters: Area under the curve (AUC)(SAD and FE- Day1, Day2, Day 3, Day 4 and day 8 post dose; MAD- Day 1 to Day 14 post dose)
- PK Parameters: half life (t1/2)(SAD and FE- Day1, Day2, Day 3, Day 4 and day 8 post dose; MAD- Day 1 to Day 14 post dose)