A Study Investigating the Safety of RO7795081 and the Effect of RO7795081 on How the Body Processes Pitavastatin and Rosuvastatin in Otherwise Healthy Overweight or Obese Adult Participants

Official title

A Phase I, Randomized, Investigator/Participant-Blind, Placebo-Controlled, Fixed-Sequence Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Orally Administered RO7795081 and the Effect of Steady-State Dose of Orally Administered RO7795081 on the Pharmacokinetics of Pitavastatin and Rosuvastatin in Otherwise Healthy Overweight or Obese Adult Participants

Overview

This is a randomized, investigator-and-participant-blind, placebo-controlled, fixed sequence, cross-over, Phase 1 study to investigate the safety, tolerability, and pharmacokinetics of multiple doses of orally administered RO7795081 and the effect of a steady-state dose of orally administered RO7795081 on the pharmacokinetics of pitavastatin and rosuvastatin in otherwise healthy, overweight or obese adult participants.

Interventions

• Drug RO7795081
  RO7795081 will be administered orally during Periods 3, 4, and 5, according to the protocol.
• Drug Placebo
  Placebo will be administered orally during Periods 3, 4, and 5, according to the protocol.
• Drug Rosuvastatin
  A single 10 mg dose of rosuvastatin (ROS) will be taken on Day 1 of Period 1 and on Day 1 of Period 4.
• Drug Pitavastatin
  A single 1 mg dose of pitavastatin (PIT) will be taken on Day 1 of Period 2 and on Day 1 of Period 5.

Primary outcome measures

• Incidence and Severity of Adverse Events [Time frame: From the first dose of study treatment until the final visit (up to 111 days)]
• Incidence of Abnormal Clinical Laboratory Test Results [Time frame: From the first dose of study treatment until the final visit (up to 111 days)]
• Incidence of Abnormal Vital Sign Assessments [Time frame: From the first dose of study treatment until the final visit (up to 111 days)]
• Incidence of Abnormal Electrocardiogram Parameters [Time frame: From the first dose of study treatment until the final visit (up to 111 days)]
• Maximum Plasma Concentration Observed (Cmax) of Rosuvastatin, Administered Alone and in Combination with RO7795081 [Time frame: Periods 1 and 4: predose and postdose at prespecified times on Days 1 to 5]
• Time to Maximum Plasma Concentration (Tmax) of Rosuvastatin, Administered Alone and in Combination with RO7795081 [Time frame: Periods 1 and 4: predose and postdose at prespecified times on Days 1 to 5]
• Area Under the Plasma Concentration-Time Curve (AUC) from Time 0 to the Last Measurable Concentration (AUClast) of Rosuvastatin, Administered Alone and in Combination with RO7795081 [Time frame: Periods 1 and 4: predose and postdose at prespecified times on Days 1 to 5]
• AUC from Time 0 to Infinity (AUCinf) of Rosuvastatin, Administered Alone and in Combination with RO7795081 [Time frame: Periods 1 and 4: predose and postdose at prespecified times on Days 1 to 5]
• Cmax of Pitavastatin, Administered Alone and in Combination with RO7795081 [Time frame: Periods 2 and 5: predose and postdose at prespecified times on Days 1 to 4]
• Tmax of Pitavastatin, Administered Alone and in Combination with RO7795081 [Time frame: Periods 2 and 5: predose and postdose at prespecified times on Days 1 to 4]

Secondary outcome measures (5)

• Plasma Concentration of RO7795081 Over Time, Administered Alone and in Combination with Rosuvastatin and Pitavastatin [Time frame: Period 3: predose and postdose at prespecified times from Days 2 to 49; Period 4: predose and postdose at prespecified times on Days 1 to 4; Periods 4: predose and postdose at prespecified times on Days 1 to 9]
• Cmax of RO7795081, Administered Alone and in Combination with Rosuvastatin and Pitavastatin [Time frame: Period 3: predose and postdose at prespecified times from Days 2 to 49; Period 4: predose and postdose at prespecified times on Days 1 to 4; Periods 4: predose and postdose at prespecified times on Days 1 to 9]
• Tmax of RO7795081, Administered Alone and in Combination with Rosuvastatin and Pitavastatin [Time frame: Period 3: predose and postdose at prespecified times from Days 2 to 49; Period 4: predose and postdose at prespecified times on Days 1 to 4; Periods 4: predose and postdose at prespecified times on Days 1 to 9]
• AUClast of RO7795081, Administered Alone and in Combination with Rosuvastatin and Pitavastatin [Time frame: Period 3: predose and postdose at prespecified times from Days 2 to 49; Period 4: predose and postdose at prespecified times on Days 1 to 4; Periods 4: predose and postdose at prespecified times on Days 1 to 9]
• AUCinf of RO7795081, Administered Alone and in Combination with Rosuvastatin and Pitavastatin [Time frame: Period 3: predose and postdose at prespecified times from Days 2 to 49; Period 4: predose and postdose at prespecified times on Days 1 to 4; Periods 4: predose and postdose at prespecified times on Days 1 to 9]

Eligibility criteria

Inclusion criteria

• Healthy participants with no clinically relevant findings on physical examination at screening and at baseline (including detailed medical and surgical history, vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis); with no suspicion of cognitive impairment or dementia as judged by the Investigator; who are not under judicial supervision, guardianship, or curatorship.
• Body Mass Index (BMI) ≥27.0 kg/m\^2 at screening and on Day -1 of Period 1
• Stable body weight (defined as <5% gain or loss) in the 2 months prior to screening as per verbal report by the participant and for the period between screening and Day -1 of Period 1 as per measured weight
• Agreement to adhere to the contraception requirements

Exclusion criteria

• Pregnant, breastfeeding, or intending to become pregnant during the study
• Any condition or disease detected during the medical interview or physical examination that would render the participant unsuitable for the study, place the participant at undue risk, or interfere with the ability of the participant to complete the study in the opinion of the Investigator
• History or presence of any clinically significant cardiovascular, broncho-pulmonary, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological, psychiatric, or metabolic disorders, allergic diseases, hypofertility, cancer, or cirrhosis
• History or evidence of any medical condition capable of significantly altering the absorption, metabolism, or elimination of drugs
• History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or CNS infections (e.g., meningitis)
• History of acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Basic science

Study locations

Netherlands · 1 center

• ICON Plc (LPRA) - Netherlands — Groningen

Identifiers

NCT: NCT06982131 · BP45800 · 2024-519277-18-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗