A Study Investigating the Effect of Different Approved Medications on How the Body Processes the Study Compound RO7795081

NCT06809608 | Completed Phase 1

• 2 other identifiers: BP456702024-517360-37-00
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, non-randomized, open-label, cross-over study in healthy male and female participants. Part 1 of the study has a 2-period (a single fixed sequence) design and will investigate the impact of itraconazole on the pharmacokinetics (PK) of RO7795081 in healthy participants. A maximum of up to 25 participants will be enrolled in Part 1 and sequentially undergo Period 1 (RO7795081 alone) followed by Period 2 (RO7795081 with itraconazole). Part 2 of the study has an adaptive design with up to 4 periods (a single fixed sequence) and will investigate the impact of gemfibrozil and cyclosporine on the PK of RO7795081 in healthy participants. A maximum of up to 25 participants will be enrolled in Part 2 and sequentially undergo Period 1 (RO7795081 alone) followed by Period 2 (RO7795081 with gemfibrozil), Period 3 (RO7795081 with cyclosporine 200 mg), and finally Period 4 (RO7795081 with cyclosporine ≤600 mg).

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (8)

• Part 1: Maximum Concentration Observed (Cmax) of RO7795081, Administered Alone and in Combination with Itraconazole

  Part 1, Period 1: Days 1 to 5 and 7; Part 1, Period 2: Days -4, -1, 1 to 10, 12, 14, 20, and 26

• Part 1: Time to Maximum Concentration Observed (Tmax) of RO7795081, Administered Alone and in Combination with Itraconazole

  Part 1, Period 1: Days 1 to 5 and 7; Part 1, Period 2: Days -4, -1, 1 to 10, 12, 14, 20, and 26

• Part 1: Area Under the Concentration-Time Curve from Time 0 to the Last Measurable Concentration (AUClast) of RO7795081, Administered Alone and in Combination with Itraconazole

  Part 1, Period 1: Days 1 to 5 and 7; Part 1, Period 2: Days -4, -1, 1 to 10, 12, 14, 20, and 26

• Part 1: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of RO7795081, Administered Alone and in Combination with Itraconazole

  Part 1, Period 1: Days 1 to 5 and 7; Part 1, Period 2: Days -4, -1, 1 to 10, 12, 14, 20, and 26

• Part 2: Cmax of RO7795081, Administered Alone and in Combination with Gemfibrozil or Cyclosporine

  Part 2, Period 1: Days 1 to 5 and 7; Part 2, Period 2: Days -3 to 5, and 7; Part 2, Period 3: Days -1 to 5, and 7; Part 2, Period 4: Days -1 to 5, 7, and 18

• Part 2: Tmax of RO7795081, Administered Alone and in Combination with Gemfibrozil or Cyclosporine

  Part 2, Period 1: Days 1 to 5 and 7; Part 2, Period 2: Days -3 to 5, and 7; Part 2, Period 3: Days -1 to 5, and 7; Part 2, Period 4: Days -1 to 5, 7, and 18

• Part 2: AUClast of RO7795081, Administered Alone and in Combination with Gemfibrozil or Cyclosporine

  Part 2, Period 1: Days 1 to 5 and 7; Part 2, Period 2: Days -3 to 5, and 7; Part 2, Period 3: Days -1 to 5, and 7; Part 2, Period 4: Days -1 to 5, 7, and 18

• Part 2: AUCinf of RO7795081, Administered Alone and in Combination with Gemfibrozil or Cyclosporine

  Part 2, Period 1: Days 1 to 5 and 7; Part 2, Period 2: Days -3 to 5, and 7; Part 2, Period 3: Days -1 to 5, and 7; Part 2, Period 4: Days -1 to 5, 7, and 18

Secondary Outcomes (7)

• Part 1: Plasma Concentrations of Itraconazole and Hydroxy-Itraconazole Over Time

  Part 1, Period 2: Days -3 to 2, 4, 6, 8, and 14

• Part 2: Plasma Concentrations of Gemfibrozil Over Time

  Part 2, Period 2: Days -1 to 2, and 4

• Part 2: Blood Concentrations of Cyclosporine Over Time

  Part 2, Period 3: Days 1 to 5, and 7; Part 2, Period 4: Days 1 to 5, and 7

• Incidence and Severity of Adverse Events

  Part 1: from first study treatment until safety follow-up visit (37 days); Part 2: from first study treatment until safety follow-up visit (56 days)

• Incidence of Abnormal Clinical Laboratory Test Findings

  Part 1: from first study treatment until safety follow-up visit (37 days); Part 2: from first study treatment until safety follow-up visit (56 days)

Study Arms (2)

Part 1: RO7795081, Then RO7795081 and Itraconazole

EXPERIMENTAL

In Part 1, Period 1 (8 days), participants will be administered a single oral dose of RO7795081 on Day 1. Washout period between Period 1 Day 1 and Period 2 Day -3: at least 7 days. In Part 1, Period 2 (26 days), participants will receive a 3-day lead-in oral administration of itraconazole (200 mg twice daily \[BID\] on Day -3 and 200 mg once daily \[QD\] on Day -2 and Day -1). On Day 1, a single oral dose of RO7795081 will be co-administered with itraconazole (200 mg QD), followed by continued itraconazole dosing (200 mg QD) from Day 2 up to and including Day 9.

Drug: RO7795081; Drug: Itraconazole

Part 2: RO7795081, Then RO7795081 and Gemfibrozil, Then RO7795081 and Cyclosporine

EXPERIMENTAL

In Part 2, Period 1 (8 days), participants will be administered a single oral dose of RO7795081 on Day 1. Washout period between Period 1 Day 1 and Period 2 Day -2: at least 7 days. In Part 2, Period 2 (10 days), participants will be co-administered a single oral dose of RO7795081 with gemfibrozil (600 mg BID) on Day 1, after a 2-day lead-in oral administration of gemfibrozil 600 mg BID (Day -2 to Day -1) followed by continued BID dosing up to and including Day 3. Washout period between Period 2 Day 1 and Period 3 Day 1: at least 7 days. In Part 2, Period 3 (8 days), participants will be co-administered a single oral dose of RO7795081 and a single oral dose of cyclosporine (200 mg) on Day 1. Washout period between Period 3 Day 1 and Period 4 Day 1: at least 7 additional days after Period 3 Day 7 (total of 14 days). In Part 2, Period 4 (18 days), participants will be co-administered a single oral dose of RO7795081 and a single oral dose of cyclosporine (600 mg or less) on Day 1.

Drug: RO7795081; Drug: Gemfibrozil; Drug: Cyclosporine

Interventions

RO7795081 DRUG

A single dose will be administered orally per study period (see arm descriptions).

Also known as: CT-996, RG6652

Part 1: RO7795081, Then RO7795081 and Itraconazole; Part 2: RO7795081, Then RO7795081 and Gemfibrozil, Then RO7795081 and Cyclosporine

Itraconazole DRUG

Administered orally (see arm description).

Part 1: RO7795081, Then RO7795081 and Itraconazole

Gemfibrozil DRUG

Administered orally (see arm description).

Part 2: RO7795081, Then RO7795081 and Gemfibrozil, Then RO7795081 and Cyclosporine

Cyclosporine DRUG

A single dose will be administered orally per study period (see arm descriptions).

Part 2: RO7795081, Then RO7795081 and Gemfibrozil, Then RO7795081 and Cyclosporine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy biological males or females, defined by absence of evidence of any active or chronic disease
• Ability to communicate with the Investigator
• Able and willing to attend the necessary visits to the study site
• Not under judicial supervision, guardianship, or curatorship
• Body mass index (BMI) of 18 to 32 kg/m\^2 inclusive, and a body weight of ≥50 kilograms at screening

You may not qualify if:

• Any condition or disease detected during the medical interview/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, bronchopulmonary, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological, psychiatric, genitourinary, metabolic disorders, allergic diseases, cancer, or cirrhosis
• History or evidence of any medical condition capable of significantly altering the absorption, metabolism, or elimination of drugs
• Surgical history of the GI tract affecting gastric motility or altering the GI tract (with the exception of uncomplicated appendectomy and cholecystectomy)
• History of malignancy in the past 5 years, except for fully treated local basal carcinoma, or fully treated carcinoma in situ of cervix
• History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or central nervous system infections (e.g., meningitis)
• Any major illness (in the opinion of the Investigator) within 1 month before the screening examination or any febrile illness (in the opinion of the Investigator) within 1 week prior to screening and within 1 week prior to admission
• History of clinically significant hypersensitivity (e.g., drugs \[including but not limited to lidocaine, caffeine, povidone-iodine\], excipients) or clinically significant allergic reactions
• Have an abnormal blood pressure at the time of screening and on baseline, confirmed by the average of 3 blood pressure measurements, properly measured with well-maintained equipment: supine systolic blood pressure \<90 millimetres of mercury (mmHg) or \>140 mmHg or diastolic blood pressure \<45 mmHg or \>90 mmHg
• Confirmed (based on the average of ≥ 3 consecutive measurements) resting pulse rate greater than 100 or less than 40 beats per minute at the time of screening and on baseline
• History or presence during screening and baseline of clinically significant ECG abnormalities before study drug administration (e.g., PQ/PR interval \>210 milliseconds (ms), QTcF \>450 ms \[\>470 ms female participants\], based on the average interval on triplicate ECGs) or cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death)
• Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel, and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility
• Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of drug of abuse (including cannabis-containing products) and/or evidence of current or previous drug of abuse (including cannabis-containing products) dependency within 5 years before screening
• Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk, or any participant with a history of suicidal or homicidal attempts
• Bipolar disorder, schizophrenia or any other serious psychiatric condition (e.g., Axis I Disorder, DSM-IV-TR)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

ICON

Groningen, 9728 NZ, Netherlands

Location

MeSH Terms

Interventions

Itraconazole; Gemfibrozil; Cyclosporine

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Volatile; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2025
• First Posted: February 5, 2025
• Study Start: February 13, 2025
• Primary Completion: June 16, 2025
• Study Completion: June 16, 2025
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)