Clinical trial NCT02972255: A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO7079901 and the Combination of RO7079901 With Meropenem in Adult Healthy Volunteers
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of RO7079901 Administered Intravenously Both Alone and in Combination With Meropenem in Adult Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-11-23
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Part I: Percentage of Participants With Adverse Events
timeFrame: From screening to the follow-up or early withdrawal visit (up to Day 15)
measure: Part II: Percentage of Participants With Adverse Events
timeFrame: From screening to the follow-up or early withdrawal visit (up to Day 17)
measure: Part III: Percentage of Participants With Adverse Events
timeFrame: From screening to the follow-up or early withdrawal visit (up to Day 17)
measure: Part I: Maximum Observed Plasma Concentration (Cmax) of RO7079901
timeFrame: Pre-infusion (0-1 hour [hr]) (infusion duration: 90 minutes [min]), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Time to Reach Cmax (Tmax) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Area Under the Plasma Concentration-Time Curve From Time Zero Until End of Dosing Interval (AUC0-tau) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Terminal Elimination Rate Constant of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Terminal Elimination Half-Life (t1/2) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Total Clearance (CL) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Volume of Distribution at Steady State (Vss) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Cmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Tmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: AUC0-tau of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Terminal Elimination Rate Constant of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: t1/2 of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Cmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Tmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: AUC0-tau of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: Terminal Elimination Rate Constant of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part I: t1/2 of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
measure: Part II - Single Dose: Cmax of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Tmax of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-tau of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Terminal Elimination Rate Constant of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: t1/2 of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: CL of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Vss of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Cmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Tmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-tau of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: t1/2 of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Cmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Tmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-tau of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: t1/2 of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Repeat Dose: Cmax of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Tmax of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: AUC0-tau of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Terminal Elimination Rate Constant of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: t1/2 of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: CL of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Vss of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Cmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Tmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: AUC0-tau of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: t1/2 of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Cmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Tmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: AUC0-tau of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part II - Repeat Dose: t1/2 of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
measure: Part I: Cumulative Amount of RO7079901 Excreted in Urine (Ae)
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Ae From Time 0 to End of the Dosing Interval (8 hrs) (Ae0-tau) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Percent of RO7079901 Dose Excreted in Urine (Ae%), Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Renal Clearance (CLr) of RO7079901, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Ae of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Ae0-tau of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Ae of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Ae0-tau of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part I: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
measure: Part II - Single Dose: Ae of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae0-tau of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae0-tau of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae0-tau of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Single Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II - Repeat Dose: Ae of RO7079901
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae0-tau of RO7079901
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae of Metabolite RO7110880
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae0-tau of Metabolite RO7110880
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae of Metabolite RO7053802
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae0-tau of Metabolite RO7053802
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Repeat Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
measure: Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Quantifiable Time-Point (AUC0-last) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-last of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-24h of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-inf of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-last of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-24h of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Single Dose: AUC0-inf of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
measure: Part II - Repeat Dose: AUC0-last of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-24h of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-inf of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-last of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-24h of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-inf of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-last of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-24h of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II - Repeat Dose: AUC0-inf of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
measure: Part II: Cumulative Amount of RO7079901 Excreted in Urine From Time 0 to 24 Hours (Ae0-24h)
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: Ae% of RO7079901, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: Ae0-24 of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: Ae0-24 of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part II: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
measure: Part III: Cmax of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Tmax of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-tau of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-last of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: AUC0-inf of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Terminal Elimination Rate Constant of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: t1/2 of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: CL of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Vss of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Cmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Tmax of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-tau of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-last of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: AUC0-inf of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Terminal Elimination Rate Constant of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: t1/2 of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Cmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Tmax of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-tau of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-last of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: AUC0-inf of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Terminal Elimination Rate Constant of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: t1/2 of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Ae of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-tau of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-24h of RO7079901
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae% of RO7079901, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae% of RO7079901, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-tau of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-24h of Metabolite RO7110880
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-tau of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-24h of Metabolite RO7053802
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Secondary outcomes:
measure: Part III: Cmax of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Tmax of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-tau of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-last of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: AUC0-inf of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Terminal Elimination Rate Constant of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: t1/2 of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: CL of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Vss of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Cmax of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Tmax of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-tau of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: AUC0-last of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: AUC0-inf of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Terminal Elimination Rate Constant of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: t1/2 of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
measure: Part III: Ae of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-tau of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-24h of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae% of Meropenem, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae% of Meropenem, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: CLr of Meropenem, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion on Day 3
measure: Part III: CLr of Meropenem, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-tau of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae0-24h of Open Ring Metabolite of Meropenem
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
measure: Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/Dose
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
measure: Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/AUC0-tau
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion on Day 3
measure: Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/AUC0-24h
timeFrame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Other outcomes:
Locations:
city: Evansville
country: United States
facility: Covance Clinical Research Unit Inc.; Covance Gfi Research
state: Indiana
city: Madison
country: United States
facility: Covance Clinical Research Unit, Inc
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Mallalieu NL, Winter E, Fettner S, Patel K, Zwanziger E, Attley G, Rodriguez I, Kano A, Salama SM, Bentley D, Geretti AM. Safety and Pharmacokinetic Characterization of Nacubactam, a Novel beta-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02229-19. doi: 10.1128/AAC.02229-19. Print 2020 Apr 21.