Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
QTcNi change from time-matched baseline measurement on Day -1 to Day 29 - supported sitting position |
Largest time-matched mean difference between cebranopadol and placebo in supported sitting QT interval corrected for heart rate using an individual correction (QTcNi) change from time-matched baseline measurement on Day -1. |
Day -1 up to Day 29 |
|
Secondary |
QTcNi change from time-matched baseline measurement on Day -1 to Day 29 - supine position |
Largest time-matched mean difference between cebranopadol and placebo in supine QTcNi change from time-matched baseline measurement on Day -1. |
Day -1 up to Day 29 |
|
Secondary |
QTcF change from time-matched baseline measurement on Day -1 to Day 29 - sitting position |
Largest time-matched mean difference between cebranopadol and placebo in supported sitting QT interval corrected for heart rate using the Fridericia formula (QTcF) change from time-matched baseline measurement on Day -1. |
Day -1 up to Day 29 |
|
Secondary |
QTcF change from time-matched baseline measurement on Day -1 to Day 29 - supine position |
Largest time-matched mean difference between cebranopadol and placebo in supine QTcF change from time-matched baseline measurement on Day -1. |
Day -1 up to Day 29 |
|
Secondary |
Pharmacokinetic parameter: AUC0-tau,ss of cebranopadol |
Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval, tau, at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-tau,ss of M2 (7-hydroxy-GRT6005) |
Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval, tau, at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-tau,ss of M3 (N-desmethyl-GRT6005) |
Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval, tau, at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-tau,ss of M6 (7-hydroxy N-desmethyl-GRT6005) |
Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval, tau, at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-t of cebranopadol |
Area under the plasma concentration versus time curve from time 0 to time t after the last dose. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-t of M2 (7-hydroxy-GRT6005) |
Area under the plasma concentration versus time curve from time 0 to time t after the last dose. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-t of M3 (N-desmethyl-GRT6005) |
Area under the plasma concentration versus time curve from time 0 to time t after the last dose. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-t of M6 (7-hydroxy N-desmethyl-GRT6005) |
Area under the plasma concentration versus time curve from time 0 to time t after the last dose. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cav,ss of cebranopadol |
Average plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cav,ss of M2 (7-hydroxy-GRT6005) |
Average plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cav,ss of M3 (N-desmethyl-GRT6005) |
Average plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cav,ss of M6 (7-hydroxy N-desmethyl-GRT6005) |
Average plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmax,ss of cebranopadol |
Maximum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmax,ss of M2 (7-hydroxy-GRT6005) |
Maximum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmax,ss of M3 (N-desmethyl-GRT6005) |
Maximum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmax,ss of M6 (7-hydroxy N-desmethyl-GRT6005) |
Maximum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmin,ss of cebranopadol |
Minimum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmin,ss of M2 (7-hydroxy-GRT6005) |
Minimum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmin,ss of M3 (N-desmethyl-GRT6005) |
Minimum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmin,ss of M6 (7-hydroxy N-desmethyl-GRT6005) |
Minimum plasma drug concentration at steady state. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Fluctuation of cebranopadol |
The difference between Cmin and Cmax standardized to Cavg, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Fluctuation of M2 (7-hydroxy-GRT6005) |
The difference between Cmin and Cmax standardized to Cavg, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Fluctuation of M3 (N-desmethyl-GRT6005) |
The difference between Cmin and Cmax standardized to Cavg, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Fluctuation of M6 (7-hydroxy N-desmethyl-GRT6005) |
The difference between Cmin and Cmax standardized to Cavg, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Swing of cebranopadol |
The difference between Cmin and Cmax standardized to Cmin, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Swing of M2 (7-hydroxy-GRT6005) |
The difference between Cmin and Cmax standardized to Cmin, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Swing of M3 (N-desmethyl-GRT6005) |
The difference between Cmin and Cmax standardized to Cmin, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Swing of M6 (7-hydroxy N-desmethyl-GRT6005) |
The difference between Cmin and Cmax standardized to Cmin, within 1 dosing interval. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: tmax of cebranopadol |
Time of maximum plasma drug concentration. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: tmax of M2 (7-hydroxy-GRT6005) |
Time of maximum plasma drug concentration. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: tmax of M3 (N-desmethyl-GRT6005) |
Time of maximum plasma drug concentration. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: tmax of M6 (7-hydroxy N-desmethyl-GRT6005) |
Time of maximum plasma drug concentration. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-inf of moxifloxacin |
Area under the plasma concentration versus time curve from time 0 to infinity. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for moxifloxacin were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: AUC0-t of moxifloxacin |
Area under the first moment of the plasma concentration versus time curve from time 0 to time t. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for moxifloxacin were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: Cmax of moxifloxacin |
Maximum plasma drug concentration. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for moxifloxacin were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: t1/2 of moxifloxacin |
Terminal half-life. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for moxifloxacin were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|
Secondary |
Pharmacokinetic parameter: tmax of moxifloxacin |
Time of maximum plasma drug concentration. PK blood samples were collected before administration of the IMP and up to 96 hours after dosing; 32 PK blood samples were obtained from each participant. Plasma concentrations for moxifloxacin were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. |
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 14, 24, 48, 72, and 96 hours post-dose |
|