The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of RO6889450 in Healthy Volunteers

NCT02699372 | Completed Phase 1

• 2 other identifiers: BP301342015-005509-35
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, single center, adaptive single ascending dose (Part 1) and multiple ascending dose (Part 2) study is designed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamics following an oral administration of RO6889450 versus placebo in healthy volunteers. The anticipated duration of this study is approximately 18 weeks.

Conditions

Healthy Volunteer

Keywords

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

• Percentage of Participants With Dose Limiting Toxicities After Single Ascending Dose (SAD) - Part 1

  up to 22 days

• Area Under the Curve from Time Zero to end of dosing interval (AUCtau) After Multiple Oral Ascending Doses - Part 2

  Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1; predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21

• Percentage of Participants With Dose Limiting Toxicities After Multiple Oral Ascending Doses (MAD) - Part 2

  up to 35 days

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 to inf)] After Single Ascending Dose - Part 1

  Part 1: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours (hr) postdose on Day 1; Day 2, 3, 4, 6, 7, 8

• RO6889450 Maximum Plasma Concentration (Cmax) After Single Oral Ascending Doses

  Part 1: predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, Days 2, 3, 4, 6, 7, 8

• RO6889450 Maximum Plasma Concentration (Cmax) After Multiple Oral Ascending Doses

  Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 14, Days 15, 16, 17, 19, 20, 21

• RO6889450 Minimum Observed Plasma Trough Concentration (Cmin)

  Part 2: predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 14, Days 15

Secondary Outcomes (40)

• Time to Reach Maximum Observed Plasma Concentration (Tmax) After Multiple Ascending Dose - Part 2

  predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose, Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21

• Terminal Rate Constant After Multiple Ascending Dose - Part 2

  Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5,1,1.5, 2, 2.5, 3,4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21

• Apparent Terminal Half-Life (t1/2) After Multiple Ascending Dose - Part 2

  Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3,4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21

• Apparent Oral Clearance (CL/F) After Multiple Ascending Dose - Part 2

  Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21

• Cumulative Amount Excreted Unchanged in Urine (Ae) After Multiple Ascending Dose - Part 2

  Part 2: predose, 0 to 6, 6 to 12, 12 to 24 hours postdose on Day 1, 14, 24 to 48 and 48 to 72 hours after Day 14 dosing

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Healthy volunteers will receive the placebo equivalent to RO6889450 as oral capsules.

Drug: Placebo

RO6889450: Part 1 Single Ascending Dose (SAD)

EXPERIMENTAL

Participants will undergo a series of screening visits prior to treatment and 4 weeks follow-up. Healthy volunteers will be enrolled in up to 7 dose groups (5 milligram \[mg\] to 450 mg) and will receive single oral dose of RO6889450 in the morning of the Day 1.

Drug: RO6889450

RO6889450: Part 2 Multiple Ascending Dose (MAD)

EXPERIMENTAL

The starting dose for Part 2 MAD will be determined by analysis of safety and pharmacokinetic data of Part 1 SAD. All participants will receive RO6889450 orally for 14 days.

Drug: RO6889450

Interventions

Placebo DRUG

Placebo

RO6889450 DRUG

RO6889450: Part 1 Single Ascending Dose (SAD); RO6889450: Part 2 Multiple Ascending Dose (MAD)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A body mass index (BMI) between 18 to 30 kilogram per square meter (kg/m\^2) inclusive
• Body weight in the range of 50 to 100 kilogram (kg) and right-handed - Part 2 only
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
• Fluent in the language of the Investigator and study staff (including raters)
• Able to participate and comply with the study restrictions

You may not qualify if:

• Part 1 and Part 2:
• Disorders of the central nervous system (CNS), psychiatric disorders, behavioral disturbances
• Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk
• Any personal or familial history (first degree) of seizures, epilepsy or other convulsive condition
• Positive family history of psychosis or mood disorders up to first degree relative
• Angle closure glaucoma, history or current significant ophthalmologic or neurologic condition that would adversely affect the pupillometry assessment
• Suspicion of regular consumption of drug of abuse and/or any history of alcohol addiction with positive urine drug screen and/or positive alcohol urine test, or regular smoker
• Positive result on hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus antibody (HIV 1 and 2)
• Any prescribed or OTC medications (including vitamins or herbal remedies) taken within 4 weeks prior to first dosing or within 5 times the elimination half-life of the medication prior to first dosing (whichever is longer)
• Taking any nutrients known to modulate CYP3A activity (e.g., grapefruit juice; Seville orange) within 2 weeks prior to administration of study drugs
• Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis)
• Participation in an investigational drug or device study within 90 days prior to screening
• Dietary restrictions that would prohibit the consumption of standardized meals
• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant in this study
• Part 2:

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

PRA Health Sciences Early Development Services

Zuidlaren, 9471 GP, Netherlands

Location

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: March 4, 2016
• Study Start: March 21, 2016
• Primary Completion: April 14, 2017
• Study Completion: April 14, 2017
• Last Updated: November 24, 2017

Record last verified: 2017-11

Locations

NL (1)