Clinical trial NCT03717064: A Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers
Official title: An Open-Label, Fixed Sequence, Two-Period Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-10-24
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is to characterize the interaction between RO7049389 and the cholesterol-lowering drug, pitavastatin, in healthy volunteers. There is no intended clinical benefit to this study. The total duration of the study for each participant is approximately 12 weeks.


Eligibility criteria: Inclusion Criteria

* Healthy, as judged by the Investigator. 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, and based on the laboratory safety test results at screening and Day -1
* Body mass index (BMI) between 18 to 30 kg/m2 (inclusive) at screening
* Female participants: 1) Must be either surgically sterile (by means of hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy) or post-menopausal for at least one year (defined as amenorrhea \>/=12 consecutive months without another cause, and confirmed by follicle-stimulating hormone (FSH) level. 2) Participants must not be pregnant or lactating.
* Male participants: 1) Female partners must not be pregnant or lactating. 2) Must agree to remain abstinent (refrain from heterosexual intercourse) or must agree to use a condom with spermicide during the treatment period and for at least 28 days after the last dose of study drug with female partners of childbearing potential. 3) Must agree to refrain from donating sperm during the treatment period and for at least 28 days after the last dose of study drug

Exclusion Criteria

* Have a history or symptoms of any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, oncologic or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study treatment; or of interfering with the interpretation of data
* Confirmed (based on the average of 3 separate resting BP measurements in a supine position, after at least 5 minutes rest) systolic BP greater than 140 or less than 90 mmHg, and diastolic BP greater than 90 or less than 50 mmHg at screening and Day -1
* Personal history or family history of congenital long QT syndrome and/or cardiac sudden death
* History of Gilbert's syndrome
* Participants 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)
* Taking any herbal medications or substances (e.g., tea) or supplements (including vitamins), or traditional Chinese medicines (TCM) or over-the-counter (OTC) medications within 14 days of first dosing or within 5 times the elimination half-life of the medication prior to first dosing, whichever is longer
* History of having received any systemic anti-neoplastic (including radiation) or immunemodulatory 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
* Are currently enrolled in or have participated in any other clinical study involving an investigational product or in any other type of medical research within the last 30 days or 5 half lives (whichever is longer)
* Donation or loss of blood or blood products in excess of 500 mL within 3 months of screening and for the duration of the study
* Positive test for drugs of abuse (including recreational drugs) and/or positive alcohol test and/or positive cotinine test at screening and on Day -1
* Positive test at screening of any of the following: Hepatitis A virus (HAV IgM Ab), hepatitis B virus (HBsAg or HBcAb), hepatitis C virus (HCV RNA or HCV Ab) or human immunodeficiency virus (HIV-1 and HIV-2 Ab)
* History of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol) and/or drug abuse within 12 months of screening
* Use of \>5 cigarettes or equivalent nicotine-containing product per day prior to screening

Primary outcomes:
measure: Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin
timeFrame: Period 1 Day 1
measure: Period 1: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin
timeFrame: Period 1 Day 1
measure: Period 1: Time to Maximum Concentration (Tmax) of Pitavastatin
timeFrame: Period 1 Day 1
measure: Period 1: Apparent Total Clearance (CL/F) of Pitavastatin
timeFrame: Period 1
measure: Period 1: Volume of Distribution (V/F) of Pitavastatin
timeFrame: Period 1 Day 1
measure: Period 1: Elimination Half-Life (T1/2) of Pitavastatin
timeFrame: Period 1 Day 1
measure: Period 2: Maximum Plasma Concentration (Cmax) of Pitavastatin
timeFrame: Period 2 Day 4
measure: Period 2: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin
timeFrame: Period 2 Day 4
measure: Period 2: Time to Maximum Concentration (Tmax) of Pitavastatin
timeFrame: Period 2 Day 4
measure: Period 2: Apparent Total Clearance (CL/F) of Pitavastatin
timeFrame: Period 2 Day 4
measure: Period 2: Volume of Distribution (V/F) of Pitavastatin
timeFrame: Period 2 Day 4
measure: Period 2: Elimination Half-Life (T1/2) of Pitavastatin
timeFrame: Period 2 Day 4
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From the start of Period 1 through safety follow-up (Period 2, Day 34)
measure: Period 2: Cmax of RO7049389
timeFrame: Period 2 Days 3-4
measure: Period 2: AUC-tau of RO7049389
timeFrame: Period 2 Days 3-4
measure: Period 1: Cmax of Pitavastatin Lactone
timeFrame: Period 1 Day 1
measure: Period 1: AUC0-inf of Pitavastatin Lactone
timeFrame: Period 1 Day 1
measure: Period 1: AUC Ratio of Pitavastatin Lactone to Pitavastatin
timeFrame: Period 1 Day 1
measure: Period 2: Cmax of Pitavastatin Lactone
timeFrame: Period 2 Day 4
measure: Period 2: AUC0-inf of Pitavastatin Lactone
timeFrame: Period 2 Day 4
measure: Period 2: AUC Ratio of Pitavastatin Lactone to Pitavastatin
timeFrame: Period 2 Day 4
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Research Unit - Daytona
state: Florida
Study officials:
affiliation: Hoffmann-LaRoche
name: Clinical Trials
role: STUDY_DIRECTOR
References: