A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO7079901 and the Combination of RO7079901 With Meropenem in Adult Healthy Volunteers

Roche

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Other: Meropenem Placebo; Other: RO7049389 Placebo; Drug: Meropenem; Drug: RO7079901

Study type: Interventional

Funder types: Industry

Identifiers

NCT02972255

NP30052

Details and patient eligibility

About

This is a randomized, double-blind, placebo-controlled, multiple-ascending dose (MAD) study that will evaluate the safety, tolerability and pharmacokinetics (PK) of RO7079901 and the combination of RO7079901 with meropenem in healthy volunteers. The study will consist of three parts (Part I, II, and III). At each dose level/cohort, a total of 8 healthy volunteers will be randomized to receive active study drug or placebo in a 3:1 ratio.

Enrollment: 46 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy male or healthy female of non-childbearing-potential
• A Body Mass Index (BMI) between 18.0 and 30.0 kilograms per square meter (kg/m^2) (inclusive) and a body weight of at least 45 kilograms (kg) at screening
• Negative urine drug and alcohol screen (barbiturates, benzodiazepines, methadone, amphetamines, methamphetamines, opiates, cocaine, cannabinoids, cotinine, and alcohol)
• Non-smokers, or former smokers, who have not smoked for at least 60 days prior to screening

Exclusion criteria

• Known history of any significant hypersensitivity or severe allergic reaction to any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams)
• History of any severe antibiotic-associated superinfections like Clostridium difficile colitis and/or frequent fungal vaginal infections
• Concurrent or history of clinically significant cardiovascular, hepatic, renal, endocrine, gastrointestinal, respiratory, psychiatric, neurologic, and/or hematological disorders
• A history or presence of malignancy (with the exception of successfully treated basal cell carcinoma); seizures, brain lesions or other significant neurological diseases
• Donation of blood (or loss of blood) greater than 500 milliliters (mL) within three months before screening
• History of Gilbert syndrome
• Any clinically significant concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the healthy volunteer in this study
• Positive test at screening of any of the following: Hepatitis A Virus Immunoglobulin M Antibody (HAV IgM Ab), Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus Ribonucleic Acid or Hepatitis C Virus Antibody (HCV RNA or HCVAb), or Human Immunodeficiency Virus Antibody (HIV Ab)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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46 participants in 6 patient groups, including a placebo group

Part I: RO7079901

Experimental group

Description:

Participants will be randomized in two dose cohorts to receive single dose of RO7079901 1000 and 2000 milligrams (mg) intravenous (IV) infusion on Days 1 through Day 7 every 8 hours (q8h), for a total of 19 doses, with the last dose administered on the morning of Day 7.

Treatment:

Drug: RO7079901

Part I: Placebo

Placebo Comparator group

Description:

Participants will be randomized in two dose cohorts to receive single dose of placebo matching to RO7079901 on Days 1 through Day 7 q8h, for a total of 19 doses, with the last dose administered on the morning of Day 7.

Treatment:

Other: RO7049389 Placebo

Part II - Single Dose and Repeat Dose: RO7079901

Experimental group

Description:

Participants will be randomized in two dose cohorts to receive single dose of RO7079901 IV infusion at a dose above the previously studied dose levels in Part I (greater than \[\>\] 2000 mg) on Day 1, with the option to extend to q8h dosing for 7 days (i.e., starting on Day 3 through Day 9); once PK, safety and tolerability have been confirmed up to 48 hrs after the single dose.

Treatment:

Drug: RO7079901

Part II - Single Dose and Repeat Dose: Placebo

Placebo Comparator group

Description:

Participants will be randomized in two dose cohorts to receive single dose placebo matching to RO7079901 on Day 1, with the option to extend to q8h dosing for 7 days (i.e., starting on Day 3 through Day 9); once PK, safety and tolerability have been confirmed up to 48 hrs after the single dose.

Treatment:

Other: RO7049389 Placebo

Part III: RO7079901 + Meropenem

Experimental group

Description:

Participants will be randomized in three dose cohorts to receive RO7079901 and Meropenem IV infusion in one of the 2 treatment sequences. Participants randomized to Sequence 1 will receive a single dose of 2000 mg meropenem IV infusion on Day 1. On Day 2, participants will receive a single dose of RO7079901 IV infusion. Participants randomized to Sequence 2 will receive a single dose of RO7079901 IV infusion on Day 1. On Day 2, participants will receive a single dose of 2000 mg meropenem IV infusion. Starting on Day 3 and continuing through Day 9 (i.e., for a total of 19 doses, last dose in the morning of Day 9) all participants will receive RO7079901 in combination with meropenem IV infusion q8h, regardless of sequence. Escalation to a maximum dose of RO7079901 5000 mg q8h may be considered on the basis of safety and tolerability data from the previous cohorts.

Treatment:

Drug: Meropenem

Drug: RO7079901

Part III: RO7079901 Placebo + Meropenem Placebo

Placebo Comparator group

Description:

Participants will be randomized in three dose cohorts to receive RO7079901 and Meropenem matching placebos in one of the 2 treatment sequences. Participants randomized to Sequence 1 will receive a single dose of placebo matching to meropenem on Day 1. On Day 2, participants will receive a single dose of placebo matching to RO7079901. Participants randomized to Sequence 2 will receive a single dose of placebo matching to RO7079901 on Day 1. On Day 2, participants will receive a single dose of placebo matching to meropenem. Starting on Day 3 and continuing through Day 9 (i.e., for a total of 19 doses, last dose in the morning of Day 9) all participants will receive RO7079901 and meropenem matching placebos q8h, regardless of sequence.

Treatment:

Other: RO7049389 Placebo

Other: Meropenem Placebo