Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The aim of this clinical study in healthy participants is to investigate the safety and tolerability of GRT0151Y after multiple oral intake of different increasing doses and to evaluate the pharmacological effects (action of the compound) by means of pupillometry (measuring the pupil size of the eye) and Cold Presser Test (measuring the pain when immersing the hand in 2 degree Celsius cold water). An additional aim of the study is to investigate the pharmacokinetics of GRT0151Y (how it is taken up into the body and how it is excreted from the body)."
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 (100 mg GRT0151Y) | Experimental | The dose of 100 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the treatment regimen will be changed to a triple daily (t.i.d) medication with 100 mg. On Day 5 the last dose of 100 mg will be administered in the morning. Matching placebo using the same dosing regimen as defined in the treatment group. |
|
| Group 2 (125 mg GRT0151Y) | Experimental | The dose of 125 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the treatment regimen will be changed to a triple daily (t.i.d) medication with 125 mg. On Day 5 the last dose of 125 mg will be administered in the morning. Matching placebo using the same dosing regimen as defined in the treatment group |
|
| Group 3 (150 mg GRT0151Y) | Experimental | The dose of 150 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the treatment regimen will be changed to a triple daily (t.i.d) medication with 150 mg. On Day 5 the last dose of 150 mg will be administered in the morning. Matching placebo using the same dosing regimen as defined in the treatment group |
|
| Group 4 (225 mg GRT0151Y) | Experimental | The dose of 150 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the dose of 225 mg will be administered twice (b.i.d.). On Day 5 the last dose of 225 mg will be administered in the morning. Matching placebo using the same dosing regimen as defined in the treatment group |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 100 mg GRT0151Y | Drug | 100 mg capsule (1 x 100 mg capsule) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events. | Number of adverse events and number of participants with adverse events. | From the first IMP administration (Day 1) to the Final Examination (Day 4 to 11 after last period). |
| Measure | Description | Time Frame |
|---|---|---|
| Pupillometry parameter: Initial pupil diameter | Pupil size (in mm) will be measured using a Compact Integrated Pupillograph (CIP). Measurements will be performed always in the same eye of the individual (preferably the left eye). The measurements will be performed under standard low-light conditions (10-15 lux). | Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Grünenthal Study Director | Grünenthal GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ASTER | Paris | 75015 | France |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Twelve volunteers (6 males and 6 females) per dose group will be randomly assigned to two treatment sequences (placebo-verum and verum-placebo, within dose-group randomized) in a ratio of 1:1. There will be a washout period of 7 to 11 days between the treatment sequences.
Not provided
Not provided
Not provided
|
| 125 mg GRT0151Y |
| Drug |
125 mg (1 x 100 mg capsule and 1 x 25 mg capsule) |
|
| 150 mg GRT0151Y | Drug | 150 mg (1 x 100 mg capsule and 1 x 50 mg capsule) |
|
| 225 mg GRT0151Y | Drug | Day 1: 150 mg (1 x 100 mg capsule and 1 x 50 mg capsule) Day 2 - 5: 225 mg (2 x 100 mg capsules and 1 x 25 mg capsule) |
|
| Matching placebo | Drug | Matching placebo capsules using the same dosing regimen as defined in the treatment groups. |
|
| Pupillometry parameter: Amplitude of constriction | Amplitude of constriction (difference between initial pupil diameter and minimum pupil diameter [mm]) | Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours |
| Pupillometry parameter: Onset latency of miosis | Onset latency of miosis (the time between begin of light stimulus and the onset of constriction [ms]) | Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours |
| Pupillometry parameter: Constriction time | Constriction time (time for maximum pupil contraction [s]) | Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours |
| Minimum plasma concentration during dosing interval τ at steady-state (Css,min) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Maximum plasma concentration during dosing interval τ at steady-state (Css,max) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Time to reach maximum plasma concentration during dosing interval τ at steady-state (tss,max) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Area under the concentration vs. time curve after the last dose (AUC) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Average plasma concentration during dosing interval τ at steady-state (Css,ave) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Peak-trough fluctuation at steady-state (PTF%) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Rate constant for the terminal log-linear phase of the concentration time data, computed as the negative slope of the regression line for the terminal linear phase of the logarithmic concentration versus time plot (λss,z) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Half-life for the terminal log-linear phase of the concentration time data (tss,1/2,z) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Apparent terminal half-life after last dose (t1/2,Z) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Apparent terminal elimination rate constant after last dose (λz) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Area under the concentration vs. time curve in dosing interval τ at steady-state (AUCss,τ) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Extrapolated part to infinity of AUCss at steady-state (AUCextr) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Extrapolated part to infinity of AUCss in percent at steady-state (AUC%extr) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Area under the concentration-time data for dosing interval τ (AUC0-τ) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Total mean time in the total volume of distribution (MRTvsys) | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Relative total clearance (CL/F)ss | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Relative volume of distribution for the terminal log-linear phase of the concentration time data (Vz/F)ss | predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5 |
| Cold Pressor Test (CPT) (AUC of pain assessment) | The dominant hand will be plunged into a 1-3 degrees Celsius circulating cold water quench for 2 minutes. By using a computer mouse with the other hand, the participant adjusted a visual analogue scale on a computer screen facing them. The scale was labelled "no pain" at one end and "maximum pain" at the other end. | Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1, 4, 11, 23, 35 and 47 hours. |
| ID | Term |
|---|---|
| D059787 | Acute Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided