Phase 1
Completed N=12
A Study on Ketoprofen Lysine Salt (KLS) + Gabapentin (GABA) vs KLS to Investigate Their Pharmacodynamic in Healthy Males
No Condition
Source: ClinicalTrials.gov NCT04802967 ↗
Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Dec 2024
Primary outcomePrimary: Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Area Under the Concentration-time Curve (AUC) From Zero to the Last Quantifiable Concentrations (AUC0-t), — 10.5; 11.1 μg*h/mL
Summary
Part A The primary objective of this study is to determine the single dose pharmacokinetics (PK) of ketoprofen lysine salt combined with gabapentin (KLS-GABA [80 mg-34 mg]) compared to KLS alone (80 mg) in healthy male subjects.
The secondary objective of this study is:
• To determine the safety and tolerability of a single oral dose of KLS-GABA (80 mg-34 mg) compared to KLS alone (80 mg) in healthy male subjects.
Part B The primary objective of this study is to determine the pharmacodynamic (PD) effects of KLS-GABA in the Intradermal (ID) capsaicin model in healthy male subjects.
The secondary objectives of this study are:
* To further investigate the safety, tolerability, and PK of single oral doses of KLS-GABA and KLS alone.
* To investigate the possible relationship between plasma levels of drug and efficacy in pain reduction.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Area Under the Concentration-time Curve (AUC) From Zero to the Last Quantifiable Concentrations (AUC0-t), |
10.5; 11.1 | — |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A):AUC From Zero to 12 Hours Postdose (AUC0-12h) |
10.3; 11.0 | — |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to 24 Hours Postdose (AUC0-24h) |
10.5; 11.2 | — |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A):AUC From Zero to 36 Hours Postdose (AUC0-36h) |
10.5; 11.2 | — |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to 48 Hours Postdose (AUC0-48h) |
10.6; 11.3 | — |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Maximum Plasma Concentration (Cmax) |
6.69; 7.97 | — |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Time to Maximum Plasma Concentration (Tmax) |
0.501; 0.542 | — |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Half-life (t1/2) |
3.77; 2.88 | — |
| PRIMARY Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B) |
11.87; 4.95; 14.36; 8.76; 23.15; 5.41 | 0.998 |
| PRIMARY Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to Infinity (AUC0-∞), |
10.7; 11.4 | — |
| SECONDARY Adverse Events (Part A) |
2; 1; 0; 0; 0; 0 | — |
| SECONDARY Subjective Rating of Pain From the ID Capsaicin Model (Part B) |
0.44; 0.88; 0.69; 0.88; 0.06; 0.00 | — |
| SECONDARY Change From Baseline of Pain Score of Hyperalgesia (NRS) by MMRM Analysis.(Part B) |
0.10; 0.94; 0.46; 0.81; 0.75; 0.79 | — |
| SECONDARY Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) |
0.000; 0.000; 0.000; 0.000; 0.000; 0.000 | — |
| SECONDARY Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) |
0.06; 0.00; 0.00; 0.00; -0.13; -0.06 | — |
| SECONDARY Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B) |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Plasma PK Concentrations (Part B) |
000; 000; 000; 000; 000; 000 | — |
| SECONDARY Adverse Events (Part B) |
7; 5; 2; 1; 8; 4 | — |
Eligibility Criteria
Inclusion Criteria
Part A
Subjects meeting the following criteria will be included in the study:
- Subject is male, of any ethnic origin.
- Subject is aged between 18 to 55 years, inclusive.
- Subject has a body mass index (BMI) of 18 to 32 kg/m2, inclusive.
- Subject is ≥50 kg.
- Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test at Screening and Day -1 in each treatment period.
- Healthy as determined by a responsible physician, based on medical evaluation including medical history, physical examinations, concomitant medication, vital signs, 12-lead ECG, and clinical laboratory evaluations.
- Subjects must use a condom during the trial and for 3 months after their final dose of trial medication, if their partner is a woman of childbearing potential. In addition, their female partner of childbearing potential must use an additional method of highly effective contraception (see Section 6.4.1) from dosing until 3 months following dosing.
- Subject is either a non-smoker or does not smoke more than 5 cigarettes per day (or equivalent e-cigarette use).
- Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Part B
Subjects meeting the following criteria will be included in the study:
- Subject is male, with a skin type compatible with capsaicin measurements.
- Subject is aged between 18 to 55 years, inclusive.
- Subject has a BMI of 18 to 32 kg/m2, inclusive.
- Subject is ≥50 kg.
- Negative SARS-CoV-2 test at Screening and Day -1.
- Healthy as determined by a responsible physician, based on medical evaluation including medical history, physical examination, concomitant medication, vital signs, 12-lead ECG, and clinical laboratory evaluations.
- Subject must be in good general health with a skin type compatible with the measures, and without significant skin allergies, pigmentary disorders, or any active dermatological conditions that might interfere with the conduct of the study.
- Subjects must use a condom during the trial and for 3 months after their final dose of trial medication, if their partner is a woman of childbearing potential. In addition, their female partner of childbearing potential must use an additional method of highly effective contraception (see Section 6.4.1) from dosing until 3 months following dosing.
- Subjects must be able to tolerate the capsaicin injection at screening.
- Demonstration of positive hyperalgesia as defined by an area of hyperalgesia ≥15 cm2 15 minutes after ID administration of 100 μg capsaicin at the additional screening visit at least 7 days prior to first dosing.
- Subject is a either non-smoker or does not smoke more than 5 cigarettes per day (or equivalent e-cigarette use).
- Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria
Part A
Subjects with any of the following will be excluded from study participation:
- Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history and physical examinations obtained during screening as judged by the Investigator (including [but not limited to], neurological, psychiatric, endocrine/diabetic, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder).
- Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), 12-lead ECG and vital signs, or physical findings at screening. In case of uncertain or questionable results, tests performed during screening may be repeated once to confirm eligibility or judged to be clinically irrelevant for healthy subjects.
- History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism and excretion (ADME
Data sourced from ClinicalTrials.gov (NCT04802967). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.