Clinical trial NCT03530917: A Study to Assess the Safety and Tolerability of Single and Multiple Ascending Doses of Oral RO7020531 in Chinese Healthy Participants.
Official title: A Randomized, Sponsor-Open, Investigator-Blinded, Subject-Blinded, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7020531 and Metabolites Following Oral Administration to Chinese Healthy Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-05-21
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of single and multiple ascending doses of oral RO7020531 in Chinese healthy participants.


Eligibility criteria: Inclusion Criteria

* Chinese healthy male and female participants. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.
* A Body Mass Index (BMI) of 19 to less than 28 kg/m2 and a body weight of at least 45 kg.
* Negative anti-nuclear antibody (ANA) test; or positive with dilutions not greater than 1:40 and with no associated history or symptoms of potential connective tissue disease or other immune-mediated diseases.
* Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods.
* Men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and refrain from donating sperm.
* Negative pregnancy test on Day -1 for female participants.
* Non-smokers, or use of \< 10 cigarettes (or equivalent nicotine-containing product) per day.

Exclusion Criteria

* Pregnant (positive pregnancy test) or lactating women, and male partners of women who are pregnant or lactating.
* History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease).
* History or symptoms of any clinically significant disease including (but not limited to), neurological, cardiovascular, endocrine, respiratory, hepatic, ocular, or renal disorder (as per Investigator's judgment).
* Personal or family history of congenital long QT syndrome or sudden cardiac death.
* Evidence of an active or suspected cancer or a history of malignancy, where in the Investigator's opinion, there is a risk of recurrence.
* History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids, IFN or PEG-IFN) within 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. Eye drop-containing and infrequent inhaled corticosteroids are permissible up to 4 weeks prior to the first dose of study drug.
* History of clinically significant thyroid disease; also, subjects with clinically significant elevated thyroid-stimulating hormone (TSH) concentrations at Screening.
* Any confirmed clinically significant allergic reactions (anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable).
* Abnormal renal function.
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values at Screening above ULN and judged clinically significant by the Investigator.
* Positive results for anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) or thyroid peroxidase antibody.
* Positive hepatitis A IgM antibody (HAV Ab IgM), hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or positive for human immunodeficiency virus (HIV) at Screening.

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Screening up until 28 days after the last dose of study drug (up to 1 year).
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805)
timeFrame: SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11.
measure: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805)
timeFrame: SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11.
measure: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805)
timeFrame: SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11.
measure: Time to Maximum Observed Plasma Concentration (Tmax) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805)
timeFrame: SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11.
measure: Half-Life (t1/2) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805)
timeFrame: SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11.
measure: Total Amount Excreted as RO7020531, RO7011785, RO7018822 and RO7033805
timeFrame: SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1
measure: Fraction Excreted as RO7020531, RO7011785, RO7018822 and RO7033805
timeFrame: SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1
measure: Renal Clearance of RO7020531, RO7011785, RO7018822 and RO7033805
timeFrame: SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1
measure: Mean Concentrations of Protein and Metabolite Markers of Humoral Response
timeFrame: SAD: Day -1, Pre-dose, 2, 6, 12, 24h Post-dose Day 1 to Day 2, 3, 5, 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20
measure: Mean Fold Changes of Protein and Metabolite Markers of Humoral Response
timeFrame: SAD: Day -1, Pre-dose, 2, 6, 12, 24, 48 (only Neopterin), 96h (only Neopterin), Post-dose Day 1 to Day 2, 3, 5, 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20
measure: Mean Fold Changes of Markers of Transcriptional Responses
timeFrame: SAD: Day -1, Pre-dose, 2, 6, 12, 24h Post-dose Day 1 to Day 2 and Day 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20
Other outcomes:
Locations:
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: