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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-005509-35 | EudraCT Number |
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This randomized, single center, adaptive single ascending dose (Part 1) and multiple ascending dose (Part 2) study is designed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamics following an oral administration of RO6889450 versus placebo in healthy volunteers. The anticipated duration of this study is approximately 18 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Healthy volunteers will receive the placebo equivalent to RO6889450 as oral capsules. |
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| RO6889450: Part 1 Single Ascending Dose (SAD) | Experimental | Participants will undergo a series of screening visits prior to treatment and 4 weeks follow-up. Healthy volunteers will be enrolled in up to 7 dose groups (5 milligram [mg] to 450 mg) and will receive single oral dose of RO6889450 in the morning of the Day 1. |
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| RO6889450: Part 2 Multiple Ascending Dose (MAD) | Experimental | The starting dose for Part 2 MAD will be determined by analysis of safety and pharmacokinetic data of Part 1 SAD. All participants will receive RO6889450 orally for 14 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug |
| ||
| RO6889450 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities After Single Ascending Dose (SAD) - Part 1 | up to 22 days | |
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) After Multiple Oral Ascending Doses - Part 2 | Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1; predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21 | |
| Percentage of Participants With Dose Limiting Toxicities After Multiple Oral Ascending Doses (MAD) - Part 2 | up to 35 days | |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 to inf)] After Single Ascending Dose - Part 1 | Part 1: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours (hr) postdose on Day 1; Day 2, 3, 4, 6, 7, 8 | |
| RO6889450 Maximum Plasma Concentration (Cmax) After Single Oral Ascending Doses | Part 1: predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, Days 2, 3, 4, 6, 7, 8 | |
| RO6889450 Maximum Plasma Concentration (Cmax) After Multiple Oral Ascending Doses | Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 14, Days 15, 16, 17, 19, 20, 21 | |
| RO6889450 Minimum Observed Plasma Trough Concentration (Cmin) | Part 2: predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 14, Days 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) After Multiple Ascending Dose - Part 2 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose, Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21 | |
| Terminal Rate Constant After Multiple Ascending Dose - Part 2 |
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Inclusion Criteria:
Exclusion Criteria:
Part 1 and Part 2:
Part 2:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Health Sciences Early Development Services | Zuidlaren | 9471 GP | Netherlands |
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| Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5,1,1.5, 2, 2.5, 3,4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21 |
| Apparent Terminal Half-Life (t1/2) After Multiple Ascending Dose - Part 2 | Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3,4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21 |
| Apparent Oral Clearance (CL/F) After Multiple Ascending Dose - Part 2 | Part 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, predose on Days 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 14, Days 15, 16, 17, 19, 20, 21 |
| Cumulative Amount Excreted Unchanged in Urine (Ae) After Multiple Ascending Dose - Part 2 | Part 2: predose, 0 to 6, 6 to 12, 12 to 24 hours postdose on Day 1, 14, 24 to 48 and 48 to 72 hours after Day 14 dosing |
| Renal Clearance (CLR) After Multiple Ascending Dose - Part 2 | Part 2: predose, 0 to 6, 6 to 12, 12 to 24 hours postdose on Day 1, 14, 24 to 48 and 48 to 72 hours after Day 14 dosing |
| Fasting Glucose Concentrations After Multiple Ascending Dose - Part 2 | Part 2: Baseline, Days 7, 15, 17 |
| Plasma Concentration of Prolactin - Part 2 | Part 2: Day 1, 14, 15 |
| Scotopic Pupil Diameter as Assessed by Pupillometer - Part 2 | Part 2: Day 1, 2, 14, 15 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) After Single Ascending Dose - Part 1 | Part 1: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours (hr) postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Last Measurable Concentration (Clast) After Single Ascending Dose - Part 1 | Part 1: predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Time to Last Measurable Concentration (Tlast) After Single Ascending Dose - Part 1 | Part 1: predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Terminal Rate Constant After Single Ascending Dose - Part 1 | Part 1: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Apparent Terminal Half-Life (t1/2) After Single Ascending Dose - Part 1 | Part 1: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours Post-Dose (AUC0-24h) After Single Ascending Dose - Part 1 | Part 1: predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUC0-last) After Single Ascending Dose - Part 1 | Part 1: predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Apparent Oral Clearance (CL/F) After Single Ascending Dose - Part 1 | Part 1: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hr postdose on Day 1, Days 2, 3, 4, 6, 7, 8 |
| Cumulative Amount Excreted Unchanged in the Urine (Ae) After Single Ascending Dose - Part 1 | Part 1: predose, 0 to 6, 6 to 12, 12 to 24 hours postdose on Day 1, 24 to 48, 48 to 72 hours after Day 1 dosing |
| Renal Clearance (CLR) After Single Ascending Dose - Part 1 | Part 1: predose, 0 to 6, 6 to 12, 12 to 24 hours postdose on Day 1, 24 to 48, 48 to 72 hours after Day 1 dosing |
| Accumulation Ratio for AUCtau (RAUC), Calculated as Day 14 AUC0-tau/Day 1 AUC0-tau - Part 2 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 hours (hr) postdose on Day 1; predose, 0.5,1,1.5, 2, 2.5, 3,4, 6, 8, 12, 16, 24 hr postdose on Day 14 |
| Accumulation Ratio for Cmax (RCmax), Calculated as Day 14 Cmax / Day 1 Cmax - Part 2 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours (hr) postdose on Day 1; predose, 0.5,1,1.5, 2, 2.5, 3,4, 6, 8, 12, 16, 24 hr postdose on Day 14 |
| Accumulation Ratio for Ctrough RCtrough, Calculated as Day 14 Ctrough / Day 1 Ctrough - Part 2 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 hours (hr) postdose on Day 1; predose, 0.5,1,1.5, 2, 2.5, 3,4, 6, 8, 12, 16, 24 hr postdose on Day 14 |
| Fasting Glucose Concentrations After Single - Part 1 | Part 1: Baseline, Day 4 |
| Change From Baseline in Glucose Level at Day 14 - Part 2 | Baseline, Day 14 |
| Change From Baseline in Insulin Level at Day 14 - Part 2 | Baseline, Day 14 |
| Change From Baseline in C-peptide Level at Day 14 - Part 2 | Baseline, Day 14 |
| Change From Baseline in Gastric Inhibitory Polypeptide (GIP) Level at Day 14 - Part 2 | Baseline, Day 14 |
| Change From Baseline in Glucagon-like Peptide-1 (GLP-1) Level at Day 14 - Part 2 | Baseline, Day 14 |
| Columbia Suicide-Severity Rating Scale (C-SSRS) Scores - Part 1 | Part 1: Day 4 |
| Columbia Suicide-Severity Rating Scale (C-SSRS) Scores - Part 2 | Part 2: Day 15 |
| Capillary Blood Glucose Levels - Part 1 | Part 1: Baseline through Day 4 |
| Capillary Blood Glucose Levels - Part 2 | Part 2: Baseline through Day 17 |
| Urine Concentration of Dopamine Metabolite - Part 2 | Baseline, Day 12, Day 13 |
| Plasma Concentration of Prolactin - Part 1 | Part 1: Day 1, Day 2 |
| Change From Baseline in Body Weight at Days 7 and 15 - Part 2 | Baseline, Day 7, 15 |
| Addiction Research Center Inventory (ARCI-49) Questionnaire Score - Part 2 | Baseline, Day 1, 7, 14 |
| Scotopic Pupil Diameter as Assessed by Pupillometer - Part 1 | Part 1: Day 1, 2 |
| Change From Baseline in Regional Cerebral Blood Flow (CBF), as Assessed by Functional Magnetic Resonance Imaging (fMRI) at Days 7 or 8, 12 or 13 | Baseline, Day 7 or 8, 12 or 13 |
| Facial Expression Recognition Task (FERT) Score, as Assessed by Emotional Test Battery (ETB) - Part 2 | Baseline, Day 12 or 13 |
| Reward Learning Task Score, as Assessed by Effort-Based Paradigms - Part 2 | Baseline, Day 12 or 13 |