Cardiovascular disease Circulatory System
Conditions
Interventions
Current intervention as of 05/11/2021:
Participants will be randomized to the treatment arms via a blinded Randomization List. In the single-ascending dose (SAD) study, each cohort will evaluate oral
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years and =65 years 2. Ability to comply with the study protocol, in the investigator’s judgment 3. Use of contraceptive measures
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 05/11/2021: 1. Pregnant or breastfeeding, or intending to become pregnant during the study or within 14 days of last study drug dose for subjects in the SAD and food effect stages and 28 days for subjects in the MAD and DDI stages 2. No comorbid conditions that may interfere with the evaluation of an investigational medical product 3. No history or evidence of substance abuse that would pose a risk to participants safety, interfere with the conduct of the study, or have an impact on the study results 4. History of severe allergic or anaphylactic reactions to human, humanized, or Current treatment with medications that are well known to prolong the QT Previous participant exclusion criteria: 1. Pregnant or breastfeeding, or intending to become pregnant during the study or within 14 days of last study drug dose for subjects in the SAD and food effect stages and 28 days for subjects in the MAD stage 2. No comorbid conditions that may interfere with the evaluation of an investigational medical product 3. No history or evidence of substance abuse that would pose a risk to participants safety, interfere with the conduct of the study, or have an impact on the study results 4. History of severe allergic or anaphylactic reactions to human, humanized, or Current treatment with medications that are well known to prolong the QT
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Incidence of adverse events (DAIDS toxicity grading scale) throughout the study 2. Vital signs (respiratory rate, pulse rate, and systolic and diastolic blood pressure, and temperature) measured at baseline and daily post-dose (Day 1-15 in the SAD and Food Effect cohorts, and Day 1- 35 in the MAD cohorts) 3. Clinical laboratory test results, including chemistry panel, hematology panel, lipid panel, coagulation panel, methemoglobin level and urinalysis measured at baseline and post dose (Day 1-15 in SAD and Food Effect cohorts, and Day 1-35 in the MAD cohorts) 4. ECG abnormalities as measured by 12-lead ECG throughout the course of the study (Day 1-15 in the SAD and Food Effect cohorts, and Day 1- 35 in the MAD cohorts) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 05/11/2021: 1. Pharmacokinetics (PK) of RO7440688 following a single and multiple doses, and the effect of food on the PK of RO7440688 following a single dose, on the basis of plasma concentrations of RO7440688 measured at specified timepoints. The following PK parameters will be calculated if data allow: 1.1. SAD stage: AUC0-24, AUC from time 0 to last quantifiable concentration (AUC0-last), AUC from time 0 to infinity (AUC0-inf), percentage of AUC extrapolated (AUC%extrap), Cmax, tmax, apparent clearance (CL/F), apparent volume of distribution during elimination phase (Vz/F), elimination rate constant (?Z), and apparent half-life (t1/2) 1.2. MAD stage: AUC0-tau, Cmax, tmax, Ctrough, average concentration at steady state (Cave,ss), peak/trough fluctuation at steady state, accumulation ratios (ARs) for Cmax and AUC0-tau on the last versus first day of dosing, CL/F, Vz/F, apparent steady-state volume of distribution (Vss/F), ?Z, and t1/2 1.3. Food effect stage: AUC0-24, AUC0-last, AUC0-inf, AUC%extrap, Cmax, tmax, CL/F, Vz/F, ?Z, t1/2, relative bioavailability of RO7440688 following a high-fat breakfast versus fasted based on AUC and Cmax, and relative bioavailability of RO7440688 following a low-fat breakfast versus fasted based on AUC and Cmax (if appropriate) 1.4 Drug-Drug Interaction stage: plasma pharmacokinetics of midazolam and its metabolite 1-hydroxy midazolam including, but not limited to AUC0-t, AUC0-inf, Cmax, tmax, CL/F, t1/2 For SAD/food effect cohorts, PK will be collected on Day 1 (predose, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h post-dose), Day 2 (24h post-dose), Day 3 (48h post-dose), Day 4 (72 post-dose), and anytime during clinic visit on Day 15. For MAD cohorts, PK will be collected on Day 1 (predose, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h post-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 5 (pre-dose), Day 7 (predose, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h post-dose), Day 8 (24h after final dose), Day 9 | — |
Countries
New Zealand
Outcome results
None listed