A Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers

An Open-Label, Fixed Sequence, Two-Period Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: RO7049389; Drug: Pitavastatin

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Research Unit - Daytona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pitavastatin; Period 1: Participants will receive a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 and up to 21 days. Period 2: Participants will receive RO7049389 on Days 1-6. Participants will also receive a single dose of pitavastatin on Day 4.	Drug: RO7049389; RO7049389 will be taken orally, in tablet form, BID on Days 1-6 of Period 2.; Drug: Pitavastatin; Pitavastatin will be taken orally, in tablet form, once on Day 1 of Period 1, and once on Day 4 of Period 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin	Period 1 Day 1
Period 1: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin	Period 1 Day 1
Period 1: Time to Maximum Concentration (Tmax) of Pitavastatin	Period 1 Day 1
Period 1: Apparent Total Clearance (CL/F) of Pitavastatin	Period 1
Period 1: Volume of Distribution (V/F) of Pitavastatin	Period 1 Day 1
Period 1: Elimination Half-Life (T1/2) of Pitavastatin	Period 1 Day 1
Period 2: Maximum Plasma Concentration (Cmax) of Pitavastatin	Period 2 Day 4
Period 2: Plasma Concentration Versus Time (Area Under the Curve, AUC0-inf) of Pitavastatin	Period 2 Day 4
Period 2: Time to Maximum Concentration (Tmax) of Pitavastatin	Period 2 Day 4
Period 2: Apparent Total Clearance (CL/F) of Pitavastatin	Period 2 Day 4
Period 2: Volume of Distribution (V/F) of Pitavastatin	Period 2 Day 4
Period 2: Elimination Half-Life (T1/2) of Pitavastatin	Period 2 Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs)	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 start of Period 1 through safety follow-up (Period 2, Day 34)
Period 2: Cmax of RO7049389		Period 2 Days 3-4
Period 2: AUC-tau of RO7049389		Period 2 Days 3-4
Period 1: Cmax of Pitavastatin Lactone		Period 1 Day 1
Period 1: AUC0-inf of Pitavastatin Lactone		Period 1 Day 1
Period 1: AUC Ratio of Pitavastatin Lactone to Pitavastatin		Period 1 Day 1
Period 2: Cmax of Pitavastatin Lactone		Period 2 Day 4
Period 2: AUC0-inf of Pitavastatin Lactone		Period 2 Day 4
Period 2: AUC Ratio of Pitavastatin Lactone to Pitavastatin		Period 2 Day 4

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Actual): December 17, 2018
• Study Completion (Actual): December 17, 2018

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2020
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pitavastatin
• Other Study ID Numbers: YP40218

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No