A Double-Blind Single-Ascending Dose (SAD) and Multiple-Ascending Dose (MAD) Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO7049389 in Healthy Chinese Participants

Hepatitis B Virus Clinical Trial

Official title:

A Randomized, Sponsor-Open, Investigator-Blinded, Subject-Blinded, Placebo-Controlled, Single-Ascending Dose (SAD) and Multiple-Ascending Dose (MAD) Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO7049389 in Healthy Chinese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03570658
• Other study ID #: YP39406
• Status: Completed
• Phase: Phase 1
• Start date: August 24, 2018
• Est. completion date: January 28, 2019

Study information

• Verified date: February 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety and tolerability of RO7049389 compared to placebo in single- and multiple-ascending doses in healthy Chinese participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: January 28, 2019
• Est. primary completion date: January 28, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria

• Chinese healthy male and female subjects, 18 to 60 years of age, inclusive.

• A Body Mass Index (BMI) of between 19 to 27 kg/m2 inclusive, and a body weight of at least 45 kg.

• Women should be of non-childbearing potential. Female subjects must be either surgically sterile (by means of hysterectomy and/or bilateral oophorectomy) or post-menopausal for at least one year (defined as amenorrhea >/=12 consecutive months without another cause, and confirmed by follicle stimulating hormone level >35 mIU/mL).

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria

• Pregnant (positive pregnancy test) or lactating women, and male subjects with partners who are pregnant or lactating.

• History or symptoms of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis.

• Personal history of congenital long QT syndrome or family history of sudden death.

• History of Gilbert's syndrome.

• History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids) </=6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.

• Subjects who have had significant acute infection, e.g., influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks of dose administration.

• Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable).

• Electrocardiogram (ECG) with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement (e.g., neuromuscular artifact that cannot be readily eliminated, arrhythmias, indistinct QTS onset, low amplitude T-wave, merged T- and U waves, prominent U-waves)

• Creatinine clearance (CrCl) </=70 mL/min (using the Cockcroft-Gault formula)

• Positive test at screening of any of the following: hepatitis A (HAV IgM Ab), hepatitis B (HBsAg), hepatitis C (HCV RNA or HCV Ab) or human immunodeficiency virus 1 and 2 (HIV Ab).

• Participation in an investigational drug or device study within 90 days prior to screening or more than 4 times per year.

• Donation or loss of blood over 500 mL within 3 months prior to screening.

• Any suspicion or history of drug and/or alcohol abuse within the last year.

• History (within 3 months of screening) of alcohol consumption exceeding two standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption will be prohibited at least 48 hours before screening, 48 hours before and 48 hours after each dose, and 48 hours before each scheduled visit.

• Use of >5 cigarettes or equivalent nicotine-containing product per day.

• Taking any prescribed or over-the-counter medications (including vitamins or herbal remedies) within 2 weeks of first dosing or within 5 times the elimination half-life of the medication prior to first dosing (whichever is longer). Occasional acetaminophen/paracetamol is allowed.

• Subjects under judicial supervision, guardianship or curatorship.

Related Conditions & MeSH terms

• Hepatitis B
• Hepatitis B Virus

Intervention

Drug:
• RO7049389
RO7049389 will be administered orally either as a single dose (SAD) or as multiple doses defined by the SAD portion of the study (MAD).
• Placebo
Placebo will be administered orally at a dose and frequency matched to RO7049389.

Locations

Country	Name	City	State
China	Huashan Hospital Affiliated to Fudan University	Shanghai City

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	From the date of first administered dose through 28 days after the last administered dose.
Secondary	Maximum Observed Plasma Concentration (Cmax) of RO7049389		At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD)
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) of RO7049389		At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD)
Secondary	Area Under the Plasma Concentration vs Time Curve to Last Measurable Concentration (AUClast) of RO7049389		At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD)
Secondary	Area Under the Plasma Concentration vs Time Curve Extrapolated to Infinity (AUC0-inf)		At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD)
Secondary	Apparent Half-Life (T1/2) of RO7049389		At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD)
Secondary	Clearance (CL/F) of RO7049389		At pre-defined intervals on Day 1 (SAD)
Secondary	Trough Plasma Concentration (Ctrough) of RO7049389		At pre-defined intervals on Day 14 (MAD)
Secondary	Accumulation Index of RO7049389		At pre-defined intervals on Day 14 (MAD)
Secondary	Area Under the Concentration vs Time Curve for a Dosing Interval (AUCtau)		At pre-defined intervals on Day 14 (MAD)