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

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ClinicalTrials.gov Identifier: NCT02972255
Recruitment Status : Completed
First Posted : November 23, 2016
Last Update Posted : May 19, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: RO7079901 Drug: Meropenem Other: RO7049389 Placebo Other: Meropenem Placebo Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : October 31, 2016
Actual Primary Completion Date : March 24, 2017
Actual Study Completion Date : March 24, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Meropenem

Arm Intervention/treatment
Experimental: Part I: RO7079901
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.
Drug: RO7079901
RO7079901 will be administered as per schedule described in individual arm.

Placebo Comparator: Part I: Placebo
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.
Other: RO7049389 Placebo
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.

Experimental: Part II - Single Dose and Repeat Dose: RO7079901
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.
Drug: RO7079901
RO7079901 will be administered as per schedule described in individual arm.

Placebo Comparator: Part II - Single Dose and Repeat Dose: Placebo
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.
Other: RO7049389 Placebo
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.

Experimental: Part III: RO7079901 + Meropenem
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.
Drug: RO7079901
RO7079901 will be administered as per schedule described in individual arm.

Drug: Meropenem
Meropenem will be administered as per schedule described in individual arm.

Placebo Comparator: Part III: RO7079901 Placebo + Meropenem Placebo
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.
Other: RO7049389 Placebo
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.

Other: Meropenem Placebo
Placebo matching to meropenem will be administered as per schedule described in individual arm.




Primary Outcome Measures :
  1. Part I: Percentage of Participants With Adverse Events [ Time Frame: From screening to the follow-up or early withdrawal visit (up to Day 15) ]
  2. Part II: Percentage of Participants With Adverse Events [ Time Frame: From screening to the follow-up or early withdrawal visit (up to Day 17) ]
  3. Part III: Percentage of Participants With Adverse Events [ Time Frame: From screening to the follow-up or early withdrawal visit (up to Day 17) ]
  4. Part I: Maximum Observed Plasma Concentration (Cmax) of RO7079901 [ Time Frame: 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 ]
  5. Part I: Time to Reach Cmax (Tmax) of RO7079901 [ Time Frame: 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 ]
  6. Part I: Area Under the Plasma Concentration-Time Curve From Time Zero Until End of Dosing Interval (AUC0-tau) of RO7079901 [ Time Frame: 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 ]
  7. Part I: Terminal Elimination Rate Constant of RO7079901 [ Time Frame: 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 ]
  8. Part I: Terminal Elimination Half-Life (t1/2) of RO7079901 [ Time Frame: 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 ]
  9. Part I: Total Clearance (CL) of RO7079901 [ Time Frame: 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 ]
  10. Part I: Volume of Distribution at Steady State (Vss) of RO7079901 [ Time Frame: 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 ]
  11. Part I: Cmax of Metabolite RO7110880 [ Time Frame: 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 ]
  12. Part I: Tmax of Metabolite RO7110880 [ Time Frame: 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 ]
  13. Part I: AUC0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  14. Part I: Terminal Elimination Rate Constant of Metabolite RO7110880 [ Time Frame: 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 ]
  15. Part I: t1/2 of Metabolite RO7110880 [ Time Frame: 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 ]
  16. Part I: Cmax of Metabolite RO7053802 [ Time Frame: 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 ]
  17. Part I: Tmax of Metabolite RO7053802 [ Time Frame: 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 ]
  18. Part I: AUC0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  19. Part I: Terminal Elimination Rate Constant of Metabolite RO7053802 [ Time Frame: 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 ]
  20. Part I: t1/2 of Metabolite RO7053802 [ Time Frame: 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 ]
  21. Part II - Single Dose: Cmax of RO7079901 [ Time Frame: 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 ]
  22. Part II - Single Dose: Tmax of RO7079901 [ Time Frame: 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 ]
  23. Part II - Single Dose: AUC0-tau of RO7079901 [ Time Frame: 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 ]
  24. Part II - Single Dose: Terminal Elimination Rate Constant of RO7079901 [ Time Frame: 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 ]
  25. Part II - Single Dose: t1/2 of RO7079901 [ Time Frame: 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 ]
  26. Part II - Single Dose: CL of RO7079901 [ Time Frame: 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 ]
  27. Part II - Single Dose: Vss of RO7079901 [ Time Frame: 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 ]
  28. Part II - Single Dose: Cmax of Metabolite RO7110880 [ Time Frame: 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 ]
  29. Part II - Single Dose: Tmax of Metabolite RO7110880 [ Time Frame: 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 ]
  30. Part II - Single Dose: AUC0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  31. Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7110880 [ Time Frame: 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 ]
  32. Part II - Single Dose: t1/2 of Metabolite RO7110880 [ Time Frame: 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 ]
  33. Part II - Single Dose: Cmax of Metabolite RO7053802 [ Time Frame: 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 ]
  34. Part II - Single Dose: Tmax of Metabolite RO7053802 [ Time Frame: 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 ]
  35. Part II - Single Dose: AUC0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  36. Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7053802 [ Time Frame: 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 ]
  37. Part II - Single Dose: t1/2 of Metabolite RO7053802 [ Time Frame: 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 ]
  38. Part II - Repeat Dose: Cmax of RO7079901 [ Time Frame: 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 ]
  39. Part II - Repeat Dose: Tmax of RO7079901 [ Time Frame: 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 ]
  40. Part II - Repeat Dose: AUC0-tau of RO7079901 [ Time Frame: 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 ]
  41. Part II - Repeat Dose: Terminal Elimination Rate Constant of RO7079901 [ Time Frame: 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 ]
  42. Part II - Repeat Dose: t1/2 of RO7079901 [ Time Frame: 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 ]
  43. Part II - Repeat Dose: CL of RO7079901 [ Time Frame: 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 ]
  44. Part II - Repeat Dose: Vss of RO7079901 [ Time Frame: 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 ]
  45. Part II - Repeat Dose: Cmax of Metabolite RO7110880 [ Time Frame: 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 ]
  46. Part II - Repeat Dose: Tmax of Metabolite RO7110880 [ Time Frame: 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 ]
  47. Part II - Repeat Dose: AUC0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  48. Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7110880 [ Time Frame: 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 ]
  49. Part II - Repeat Dose: t1/2 of Metabolite RO7110880 [ Time Frame: 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 ]
  50. Part II - Repeat Dose: Cmax of Metabolite RO7053802 [ Time Frame: 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 ]
  51. Part II - Repeat Dose: Tmax of Metabolite RO7053802 [ Time Frame: 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 ]
  52. Part II - Repeat Dose: AUC0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  53. Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7053802 [ Time Frame: 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 ]
  54. Part II - Repeat Dose: t1/2 of Metabolite RO7053802 [ Time Frame: 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 ]
  55. Part I: Cumulative Amount of RO7079901 Excreted in Urine (Ae) [ Time Frame: 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 ]
  56. Part I: Ae From Time 0 to End of the Dosing Interval (8 hrs) (Ae0-tau) of RO7079901 [ Time Frame: 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 ]
  57. Part I: Percent of RO7079901 Dose Excreted in Urine (Ae%), Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  58. Part I: Renal Clearance (CLr) of RO7079901, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  59. Part I: Ae of Metabolite RO7110880 [ Time Frame: 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 ]
  60. Part I: Ae0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  61. Part I: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  62. Part I: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  63. Part I: Ae of Metabolite RO7053802 [ Time Frame: 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 ]
  64. Part I: Ae0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  65. Part I: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  66. Part I: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  67. Part II - Single Dose: Ae of RO7079901 [ Time Frame: 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 ]
  68. Part II - Single Dose: Ae0-tau of RO7079901 [ Time Frame: 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 ]
  69. Part II - Single Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  70. Part II - Single Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  71. Part II - Single Dose: Ae of Metabolite RO7110880 [ Time Frame: 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 ]
  72. Part II - Single Dose: Ae0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  73. Part II - Single Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  74. Part II - Single Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  75. Part II - Single Dose: Ae of Metabolite RO7053802 [ Time Frame: 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 ]
  76. Part II - Single Dose: Ae0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  77. Part II - Single Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  78. Part II - Single Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  79. Part II - Repeat Dose: Ae of RO7079901 [ Time Frame: 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 ]
  80. Part II - Repeat Dose: Ae0-tau of RO7079901 [ Time Frame: 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 ]
  81. Part II - Repeat Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  82. Part II - Repeat Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  83. Part II - Repeat Dose: Ae of Metabolite RO7110880 [ Time Frame: 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 ]
  84. Part II - Repeat Dose: Ae0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  85. Part II - Repeat Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  86. Part II - Repeat Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  87. Part II - Repeat Dose: Ae of Metabolite RO7053802 [ Time Frame: 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 ]
  88. Part II - Repeat Dose: Ae0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  89. Part II - Repeat Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  90. Part II - Repeat Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  91. Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Quantifiable Time-Point (AUC0-last) of RO7079901 [ Time Frame: 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 ]
  92. Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h) of RO7079901 [ Time Frame: 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 ]
  93. Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7079901 [ Time Frame: 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 ]
  94. Part II - Single Dose: AUC0-last of Metabolite RO7110880 [ Time Frame: 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 ]
  95. Part II - Single Dose: AUC0-24h of Metabolite RO7110880 [ Time Frame: 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 ]
  96. Part II - Single Dose: AUC0-inf of Metabolite RO7110880 [ Time Frame: 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 ]
  97. Part II - Single Dose: AUC0-last of Metabolite RO7053802 [ Time Frame: 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 ]
  98. Part II - Single Dose: AUC0-24h of Metabolite RO7053802 [ Time Frame: 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 ]
  99. Part II - Single Dose: AUC0-inf of Metabolite RO7053802 [ Time Frame: 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 ]
  100. Part II - Repeat Dose: AUC0-last of RO7079901 [ Time Frame: 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 ]
  101. Part II - Repeat Dose: AUC0-24h of RO7079901 [ Time Frame: 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 ]
  102. Part II - Repeat Dose: AUC0-inf of RO7079901 [ Time Frame: 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 ]
  103. Part II - Repeat Dose: AUC0-last of Metabolite RO7110880 [ Time Frame: 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 ]
  104. Part II - Repeat Dose: AUC0-24h of Metabolite RO7110880 [ Time Frame: 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 ]
  105. Part II - Repeat Dose: AUC0-inf of Metabolite RO7110880 [ Time Frame: 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 ]
  106. Part II - Repeat Dose: AUC0-last of Metabolite RO7053802 [ Time Frame: 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 ]
  107. Part II - Repeat Dose: AUC0-24h of Metabolite RO7053802 [ Time Frame: 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 ]
  108. Part II - Repeat Dose: AUC0-inf of Metabolite RO7053802 [ Time Frame: 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 ]
  109. Part II: Cumulative Amount of RO7079901 Excreted in Urine From Time 0 to 24 Hours (Ae0-24h) [ Time Frame: 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 ]
  110. Part II: Ae% of RO7079901, Calculated as Ae0-24h/Dose [ Time Frame: 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 ]
  111. Part II: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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 ]
  112. Part II: Ae0-24 of Metabolite RO7110880 [ Time Frame: 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 ]
  113. Part II: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose [ Time Frame: 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 ]
  114. Part II: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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 ]
  115. Part II: Ae0-24 of Metabolite RO7053802 [ Time Frame: 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 ]
  116. Part II: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose [ Time Frame: 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 ]
  117. Part II: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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 ]
  118. Part III: Cmax of RO7079901 [ Time Frame: 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 ]
  119. Part III: Tmax of RO7079901 [ Time Frame: 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 ]
  120. Part III: AUC0-tau of RO7079901 [ Time Frame: 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 ]
  121. Part III: AUC0-last of RO7079901 [ Time Frame: 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) ]
  122. Part III: AUC0-inf of RO7079901 [ Time Frame: 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) ]
  123. Part III: Terminal Elimination Rate Constant of RO7079901 [ Time Frame: 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 ]
  124. Part III: t1/2 of RO7079901 [ Time Frame: 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 ]
  125. Part III: CL of RO7079901 [ Time Frame: 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 ]
  126. Part III: Vss of RO7079901 [ Time Frame: 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 ]
  127. Part III: Cmax of Metabolite RO7110880 [ Time Frame: 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 ]
  128. Part III: Tmax of Metabolite RO7110880 [ Time Frame: 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 ]
  129. Part III: AUC0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  130. Part III: AUC0-last of Metabolite RO7110880 [ Time Frame: 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) ]
  131. Part III: AUC0-inf of Metabolite RO7110880 [ Time Frame: 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) ]
  132. Part III: Terminal Elimination Rate Constant of Metabolite RO7110880 [ Time Frame: 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 ]
  133. Part III: t1/2 of Metabolite RO7110880 [ Time Frame: 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 ]
  134. Part III: Cmax of Metabolite RO7053802 [ Time Frame: 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 ]
  135. Part III: Tmax of Metabolite RO7053802 [ Time Frame: 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 ]
  136. Part III: AUC0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  137. Part III: AUC0-last of Metabolite RO7053802 [ Time Frame: 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) ]
  138. Part III: AUC0-inf of Metabolite RO7053802 [ Time Frame: 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) ]
  139. Part III: Terminal Elimination Rate Constant of Metabolite RO7053802 [ Time Frame: 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 ]
  140. Part III: t1/2 of Metabolite RO7053802 [ Time Frame: 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 ]
  141. Part III: Ae of RO7079901 [ Time Frame: 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 ]
  142. Part III: Ae0-tau of RO7079901 [ Time Frame: 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 ]
  143. Part III: Ae0-24h of RO7079901 [ Time Frame: 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) ]
  144. Part III: Ae% of RO7079901, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  145. Part III: Ae% of RO7079901, Calculated as Ae0-24h/Dose [ Time Frame: 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) ]
  146. Part III: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  147. Part III: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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) ]
  148. Part III: Ae of Metabolite RO7110880 [ Time Frame: 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 ]
  149. Part III: Ae0-tau of Metabolite RO7110880 [ Time Frame: 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 ]
  150. Part III: Ae0-24h of Metabolite RO7110880 [ Time Frame: 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) ]
  151. Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  152. Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose [ Time Frame: 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) ]
  153. Part III: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  154. Part III: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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) ]
  155. Part III: Ae of Metabolite RO7053802 [ Time Frame: 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 ]
  156. Part III: Ae0-tau of Metabolite RO7053802 [ Time Frame: 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 ]
  157. Part III: Ae0-24h of Metabolite RO7053802 [ Time Frame: 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) ]
  158. Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  159. Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose [ Time Frame: 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) ]
  160. Part III: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  161. Part III: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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 Outcome Measures :
  1. Part III: Cmax of Meropenem [ Time Frame: 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 ]
  2. Part III: Tmax of Meropenem [ Time Frame: 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 ]
  3. Part III: AUC0-tau of Meropenem [ Time Frame: 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 ]
  4. Part III: AUC0-last of Meropenem [ Time Frame: 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) ]
  5. Part III: AUC0-inf of Meropenem [ Time Frame: 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) ]
  6. Part III: Terminal Elimination Rate Constant of Meropenem [ Time Frame: 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 ]
  7. Part III: t1/2 of Meropenem [ Time Frame: 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 ]
  8. Part III: CL of Meropenem [ Time Frame: 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 ]
  9. Part III: Vss of Meropenem [ Time Frame: 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 ]
  10. Part III: Cmax of Open Ring Metabolite of Meropenem [ Time Frame: 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 ]
  11. Part III: Tmax of Open Ring Metabolite of Meropenem [ Time Frame: 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 ]
  12. Part III: AUC0-tau of Open Ring Metabolite of Meropenem [ Time Frame: 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 ]
  13. Part III: AUC0-last of Open Ring Metabolite of Meropenem [ Time Frame: 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) ]
  14. Part III: AUC0-inf of Open Ring Metabolite of Meropenem [ Time Frame: 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) ]
  15. Part III: Terminal Elimination Rate Constant of Open Ring Metabolite of Meropenem [ Time Frame: 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 ]
  16. Part III: t1/2 of Open Ring Metabolite of Meropenem [ Time Frame: 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 ]
  17. Part III: Ae of Meropenem [ Time Frame: 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 ]
  18. Part III: Ae0-tau of Meropenem [ Time Frame: 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 ]
  19. Part III: Ae0-24h of Meropenem [ Time Frame: 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) ]
  20. Part III: Ae% of Meropenem, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  21. Part III: Ae% of Meropenem, Calculated as Ae0-24h/Dose [ Time Frame: 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) ]
  22. Part III: CLr of Meropenem, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  23. Part III: CLr of Meropenem, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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) ]
  24. Part III: Ae of Open Ring Metabolite of Meropenem [ Time Frame: 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 ]
  25. Part III: Ae0-tau of Open Ring Metabolite of Meropenem [ Time Frame: 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 ]
  26. Part III: Ae0-24h of Open Ring Metabolite of Meropenem [ Time Frame: 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) ]
  27. Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/Dose [ Time Frame: 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 ]
  28. Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/Dose [ Time Frame: 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) ]
  29. Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/AUC0-tau [ Time Frame: 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 ]
  30. Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/AUC0-24h [ Time Frame: 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02972255


Locations
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United States, Indiana
Covance Clinical Research Unit Inc.; Covance Gfi Research
Evansville, Indiana, United States, 47710
United States, Wisconsin
Covance Clinical Research Unit, Inc
Madison, Wisconsin, United States, 53704
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02972255    
Other Study ID Numbers: NP30052
First Posted: November 23, 2016    Key Record Dates
Last Update Posted: May 19, 2017
Last Verified: May 2017
Additional relevant MeSH terms:
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Meropenem
Anti-Bacterial Agents
Anti-Infective Agents