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| ID | Type | Description | Link |
|---|---|---|---|
| PK872A | Other Identifier | Sponsor |
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The purpose of this study is to determine the maximum dose of GRT0151Y that is tolerable and to explore the safety profile of the drug.
For each Treatment Period (Visits 2-5), dosing will be separated by at least one week. Participants in this study will receive up to four doses of the study drug and up to two placebo (an inactive substance) preparations, one at a time on each of up to six visits. Participants will receive a single dose of either GRT0151Y or placebo beginning with the lowest dose of study drug 150 milligrams (mg), followed by 200 mg, 250 mg, 300 mg, 350 mg and 400 mg doses of the study drug. Participants will only be allowed to proceed to the next higher dose of GRT0151Y (or placebo) if the previous dose was well tolerated. Neither the participant nor the study staff will know whether participants are receiving GRT0151Y or placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GRT0151Y dose escalation | Experimental | GRT0151Y will be administered to participants as 50 mg capsules in a dose escalation range of 150, 200, 250, 300, 350 and 400 mg. Dose levels were increased by increments of 50 mg to a maximum of 400 mg, only after the previous dose level was found to be well-tolerated. During each treatment period, participants randomly received either GRT0151Y or matching placebo, in a manner that no participant received placebo in two consecutive periods. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GRT0151Y dose escalation | Drug | Single doses of 150, 200, 250, 300, 350 and 400 mg (3, 4, 5, 6, 7 or 8 capsules of 50 mg) |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of GRT0151Y | The progression to the next higher dose group occurred only after a thorough risk-benefit assessment, based upon the safety and tolerability data of the participants from the completed trial group (interim safety report [ISR]). The ISRs were prepared by the investigator and were submitted to the sponsor for benefit-risk assessment. The MTD would have been reached if the benefit-risk assessment had been unfavorable to progress to the next higher dose group. | First dose to Last dose assessed to be well tolerated. From Day 1 to Day 3 (for up to 6 periods) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed plasma concentration (Cmax) of GRT0151Y | Blood samples were obtained and plasma concentrations were determined using a validated stereoselective liquid chromatography-tandem mass spectrometry (LC-MS/MS). | pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 32 and 48 hours post dose |
| Time to reach maximum plasma concentration (tmax) of GRT0151Y |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Grünenthal Study Director | Grünenthal GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ventana Clinical Research Corporation | Toronto | Ontario | M5V 2T3 | Canada |
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During each treatment period, participants randomly received either GRT0151Y or matching placebo, in a manner that no participant received placebo in two consecutive periods.
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| Matching placebo | Drug | Matching placebo capsules (3, 4, 5, 6, 7 or 8 capsules) |
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Blood samples were obtained and plasma concentrations were determined using a validated stereoselective LC-MS/MS. |
| pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 32 and 48 hours post dose |
| Area under the plasma concentration-time curve (AUC0-t) | Blood samples were obtained and plasma concentrations were determined using a validated stereoselective LC-MS/MS. | pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 32 and 48 hours post dose |
| Divided Attention Test (DAT) | Manual-tracking test with a simultaneous visual target detection component. Participant is provided with joystick and presented with the image of an airplane and a randomly curving road; participant has to position the airplane over the center of the road while being distracted repeatedly by visual targets they have to respond to. Percentage of time over the road (milliseconds), response latency of correct responses and percentage of target hits are recorded. | pre-dose, and 1, 2, 4, 6, 8, 12, 24, 32 and 48 hours post-dose |
| Choice Reaction Time (CRT) | Choice reaction time (CRT) is a computerized assessment that trains the participant to respond to stimuli presented on the screen. The task requires the participant to react as soon as a colored key appears in one of up to eight locations. The participant must respond by lifting their finger from the central start button and depressing the corresponding response key as quickly as possible. This is the reaction time (RT). Lower scores indicate better performance. | pre-dose, and 1, 2, 4, 6, 8, 12, 24, 32 and 48 hours post-dose |
| ID | Term |
|---|---|
| D010146 | Pain |
| D059787 | Acute Pain |
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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