A Study on Ketoprofen Lysine Salt (KLS) + Gabapentin (GABA) vs KLS to Investigate Their Pharmacodynamic in Healthy Males

A Phase I, Double-Blind, PK, Safety, Tolerability Study of KSL + KLS-GABA vs KLS Alone in Healthy Males (Part A) Followed by a Study to Investigate the PD of KLS and KLS + GABA in Healthy Males (Part B)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04802967

Enrollment

141

Registered

2021-03-17

Start date

2021-02-08

Completion date

2022-04-25

Last updated

2024-12-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

No Condition

Keywords

Male healthy volunteers

Brief 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.

Detailed description

This is a Phase I, Double-Blind, Pharmacokinetic, Safety and Tolerability Study of Ketoprofen Lysine Salt Combined with Gabapentin (KLS-GABA) Compared to Ketoprofen Lysine Salt (KLS) Alone in Healthy Male Subjects (Part A) Followed by a Randomised, Double-Blind, Placebo-Controlled Study to Investigate the Pharmacodynamic Effects of KLS, and KLS in Combination with Gabapentin (GABA), in Healthy Male Subjects Using the Intradermal (ID) Capsaicin Model (Part B). Part A is a randomized, double-blind, crossover group study to investigate the safety, tolerability, and PK profile of a single oral dose of KLS-GABA compared to KLS alone in healthy male subjects. It is planned to enroll 12 subjects. All subjects take part in 2 treatment periods, in which they are randomized to receive either a single dose of KLS-GABA (80 mg-34 mg) or a single dose of KLS (80 mg) alone in each treatment period. Subjects' participation in Part A lasts approximately 7 weeks and will consist of the following: * A screening visit (up to 28 days prior to Day 1 of Treatment Period 1), * Admission to the clinical research unit (CRU) on Day -1 prior to Treatment Period 1, * Treatment Period 1 (Day 1 to Day 3), * A washout period of a minimum of 7 days, * Admission to the CRU on Day -1 prior to Treatment Period 2, * Treatment Period 2 (Day 1 to Day 3), * A follow-up visit (5 to 7 days post-final dose following Treatment Period 2). Safety will is assessed through Adverse Events (AE) reporting, 12-lead ECGs, vital signs, physical examinations, and clinical laboratory examinations. Pharmacokinetics are assessed by blood sampling. Part A treatment lasts 2 days (Day 1 in Treatment Period 1; Day 1 in Treatment Period 2) Part B is a randomized, double-blind, placebo-controlled parallel-group study to investigate the PD effects, PK/PD correlation, safety, and tolerability of three single oral dose levels of KLS-GABA compared to KLS alone, 300 mg gabapentin and placebo in the ID capsaicin model in healthy male subjects. It is planned to enroll 128 subjects, randomized evenly to 8 possible treatments; subjects receive either KLS alone, KLS-GABA, 300 mg gabapentin or placebo. The planned treatments are: * KLS alone (40 mg, 80 mg, or 160 mg) * KLS-GABA (40 mg-17 mg, 80 mg-34 mg or 160 mg-68 mg) * Gabapentin (300 mg) * Placebo Subjects' participation in Part B lasts approximately 6 weeks and consists of the following: * A screening visit (up to 28 days prior to dosing) * An additional screening visit (at least 7 days prior to dosing) to determine the subject's response to capsaicin and to familiarise them in the pain measurements, * Admission to the CRU on Day -1, for collection of pain measurements and completion of the ID capsaicin model * A treatment period (morning of Day 1 until 12 hours postdose) * Discharge from the CRU 12 hours postdose * A follow-up visit (5 to 7 days postdose). Safety is assessed through AE reporting, 12-lead ECGs, vital signs, physical examinations, and clinical laboratory examinations. Pharmacokinetics are assessed by blood sampling. Pharmacodynamics are assessed using the ID capsaicin model and pain measurements. Part B treatment lasts 1 day (Day 1).

Interventions

DRUGKetoprofen Lysine Salt combined with Gabapentin

KLS-GABA (80 mg-34 mg) in Part A and KLS-GABA (40 mg-17 mg or 80 mg-34 mg or 160 mg-68 mg) in Part B

DRUGKetoprofen Lysine Salt

KLS (80 mg) alone in each treatment period in Part A and KLS alone (40 mg, 80 mg, or 160 mg) in Part B

DRUGGabapentin

300 mg

OTHERPlacebo

2 capsules to maintain the blind

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

This study will be double-blinded (Investigator- and subject-blinded).

Intervention model description

In the Part B of the study the Intradermal (ID) Capsaicin Model is used.

Eligibility

Sex/Gender

MALE

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

Part A Subjects meeting the following criteria will be included in the study: 1. Subject is male, of any ethnic origin. 2. Subject is aged between 18 to 55 years, inclusive. 3. Subject has a body mass index (BMI) of 18 to 32 kg/m2, inclusive. 4. Subject is ≥50 kg. 5. Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test at Screening and Day -1 in each treatment period. 6. 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. 7. 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. 8. Subject is either a non-smoker or does not smoke more than 5 cigarettes per day (or equivalent e-cigarette use). 9. 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: 1. Subject is male, with a skin type compatible with capsaicin measurements. 2. Subject is aged between 18 to 55 years, inclusive. 3. Subject has a BMI of 18 to 32 kg/m2, inclusive. 4. Subject is ≥50 kg. 5. Negative SARS-CoV-2 test at Screening and Day -1. 6. 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. 7. 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. 8. 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. 9. Subjects must be able to tolerate the capsaicin injection at screening. 10. 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. 11. Subject is a either non-smoker or does not smoke more than 5 cigarettes per day (or equivalent e-cigarette use). 12. 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: 1. 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). 2. 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. 3. 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) of the study drugs. 4. Any other concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study as outlined in this Protocol, safety of the subject as per the SmPC of KLS and gabapentin (Neurontin 300 mg hard capsules) or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study. 5. Subject has a history of neurological disorders which may impact the perception of pain or impairs the subject's ability to fully participate in the study. 6. Subject has a significant skin allergy, pigmentary disorder, or any active dermatological condition. 7. AST, ALT, gamma-glutamyl transferase (GGT) or total bilirubin levels above the ULN at screening. These laboratory evaluations may be repeated once at the discretion of the Investigator. If the repeat test is within the reference range, the subject may be included only if the Investigator considers that the previous finding will not introduce additional risk factors and will not interfere with interpretation of safety data. 8. Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (anti- HCV) or human immunodeficiency virus I and II antibodies (anti-HIV I/II) at screening. 9. Positive urine test for drugs of abuse or alcohol breath test at screening or Day -1 of each treatment period. 10. History of drug and/or alcohol abuse/dependence, or intake of \>28 units of alcohol weekly, and the inability to refrain from alcohol use from 48 hours before screening and each scheduled visit until discharge from the CRU. One unit is equivalent to a 285 mL glass of full strength beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine. 11. Habitual and heavy consumption of caffeinated beverages (\>8 cups of coffee or equivalent per day) at screening; and/or unable to refrain from use of (methyl) xanthine (e.g., coffee, tea, cola, chocolate) from 48 hours prior to dosing until discharge from the CRU. 12. The subject has participated in a clinical study and has received a medication or a new chemical entity within 3 months or 5 half-lives (whichever is longer) prior to dosing of current study medication. 13. Use of any prescription or non-prescription medications, including herbal and nutritional supplements (including St. John's wort), or OTC medications (e.g., ibuprofen, aspirin) within 14 days of dosing and throughout the study. By exception, the subject may take acetaminophen (less or equal 2 g/day) for up to 48 hours prior to dosing. The Investigator and study team may review medication on a case-by-case basis to determine if its use would compromise subject safety or interfere with study procedures or data interpretation. 14. History of severe adverse reactions or allergies, or history of an anaphylactic reaction to prescription medications, non-prescription medication, food, NSAIDs or gabapentin (non-active hay-fever is acceptable). 15. Consumption of any food or drinks containing cranberry, pomegranate, starfruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges (including marmalade and juices made from these fruits) within 14 days before admission to the CRU until the end of the study. 16. Strenuous exercise within 48 hours prior to each blood collection for clinical laboratory tests. 17. Donation of blood or plasma of \>500 mL within 3 months prior to first dosing, or subject intends to donate blood during the study. 18. Male subject who will not abstain from sperm donation between dosing and 3 months after final dosing. 19. Any degree of previous or known hypersensitivity to the active substance or the excipients of the IMP. Part B Subjects with any of the following will be excluded from study participation: 1. 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). 2. 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. 3. Has a skin trauma, any active skin disorder, significant scarring, significant skin allergy, pigmentary disorder, active dermatological condition, skin disease or tattoos on either forearm, or a significant history of trauma or skin disease in either arm. 4. Subject has a known intolerance to capsaicin, hot peppers, or any excipient in the IMP. 5. Subject has active chronic pain condition(s) or a history of chronic pain conditions. 6. History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the ADME of the study drug. 7. Any other concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study as outlined in this Protocol, safety of the subject as per the SmPCs of KLS and gabapentin (Neurontin 300 mg hard capsules) or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study. 8. Subject has a history of neurological disorders which may impact the perception of pain or impairs the subject's ability to fully participate in the study. 9. AST, ALT, GGT or total bilirubin levels above the ULN at screening. These laboratory evaluations may be repeated once at the discretion of the Investigator. If the repeat test is within the reference range, the subject may be included only if the Investigator considers that the previous finding will not introduce additional risk factors and will not interfere with interpretation of safety data. 10. Positive test for HBsAg, anti-HCV or anti-HIV I/II at screening. 11. Positive urine test for drugs of abuse or alcohol breath test at screening. 12. History of drug and/or alcohol abuse/dependence, or intake of \>28 units of alcohol weekly, and the inability to refrain from alcohol use from 48 hours before Screening and each scheduled visit until discharge from the CRU. One unit is equivalent to a 285 mL glass of full strength beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine. 13. Habitual and heavy consumption of caffeinated beverages (\>8 cups of coffee or equivalent per day) at screening; and/or unable to refrain from use of (methyl) xanthine (e.g., coffee, tea, cola, chocolate) from 48 hours prior to dosing until discharge from the CRU. 14. The subject has participated in a clinical study and has received a medication or a new chemical entity within 3 months or 5 half-lives (whichever is longer) prior to dosing of current study medication. 15. Use of any prescription or non-prescription medications, including herbal and nutritional supplements (including St. John's wort), or OTC medications (e.g., ibuprofen, aspirin) within 14 days of dosing and throughout the study. By exception, the subject may take acetaminophen (less or equal 2 g/day) for up to 48 hours prior to dosing. The Investigator and study team may review medication on a case-by-case basis to determine if its use would compromise subject safety or interfere with study procedures or data interpretation. 16. History of severe adverse reactions or allergies, or history of an anaphylactic reaction to prescription medication, non-prescription medication, food, NSAIDs, gabapentin, (non-active hay-fever is acceptable), the planned local anaesthesia/analgesic regimens, ethylenediaminetetraacetic acid, Kolliphor HS 15, butylated hydroxytoluene, or capsaicin. 17. Known hypersensitivity or allergy to any component of the placebo capsules. 18. Consumption of any food or drinks containing cranberry, pomegranate, starfruit, grapefruit, pomelos, exotic citrus fruits, or Seville oranges (including marmalade and juices made from these fruits) within 14 days before admission to the CRU until the end of the study. 19. Strenuous exercise within 48 hours prior to each blood collection for clinical laboratory tests. 20. Subject has participated in a clinical study involving administration of capsaicin within 12 months of the screening visit. 21. Donation of blood or plasma of \>500 mL within 3 months prior to dosing, or subject intends to donate blood during the study. 22. Male subject who will not abstain from sperm donation between dosing and 3 months after dosing. 23. Any degree of previous or known hypersensitivity to the active substance or the excipients of the IMP.

Design outcomes

Primary

Measure	Time frame	Description
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to Infinity (AUC0-∞),	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. AUC0-∞ - area under the concentration versus time curve from time zero to infinity The area under the concentration-time curve estimated from time zero to infinity as the sum of the two areas: AUC0-t and AUCextrap, where AUCextrap is calculated as Ct / z. Estimates will be considered to be unreliable if the extrapolated area (AUCextrap) is \>20%.
Plasma PK Concentrations and Parameters of Ketoprofen (Part A):AUC From Zero to 12 Hours Postdose (AUC0-12h)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. The area under the concentration versus time curve from time zero to 12 h post-dose, calculated by the linear up-log down trapezoidal method.
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to 24 Hours Postdose (AUC0-24h)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. The area under the concentration versus time curve from time zero to 24 h post-dose, calculated by the linear up-log down trapezoidal method.
Plasma PK Concentrations and Parameters of Ketoprofen (Part A):AUC From Zero to 36 Hours Postdose (AUC0-36h)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed.The area under the concentration versus time curve from time zero to 36 h post-dose, calculated by the linear up-log down trapezoidal method.
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Maximum Plasma Concentration (Cmax)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. Is defined Cmax the maximum observed concentration.
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to 48 Hours Postdose (AUC0-48h)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed.The area under the concentration versus time curve from time zero to 48 h post-dose, calculated by the linear up-log down trapezoidal method.
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Time to Maximum Plasma Concentration (Tmax)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. Is defined T max the time at which Cmax was apparent.
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Half-life (t1/2)	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. Is defined T1/2 The apparent terminal half-life, calculated from Log e 2 / z.
Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	Day 1 at 15, 30, 60, 90 and 120 minutes post injection	The area of mechanical hyperalgesia was assessed using a standard 24 g von Frey hair. The von Frey hair was applied at 1-second intervals along each of the 4 lines intersecting at the injection site drawn onto the skin before the injection. Stimulation began distal from the injection site and advanced in 1 cm increments toward the injection site until a pain response was elicited. Subjects were asked to report when the von Frey hair first began to cause any pain sensation or discomfort and the distance of that point from the injection site in centimetres for each line at each timepoint was recorded.
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),	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose	PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. Outcome measure at 0h,16h,24h,36h, and 48h postdose below limit of quantification (0.04 μg/mL). The area under the concentration versus time curve from time zero to the last quantifiable concentration (C-last), calculated by the linear up-log down trapezoidal method; i.e. when concentrations are increasing (as in the absorption phase), the linear trapezoidal method is used, when concentrations are decreasing (as in the elimination phase), the logarithmic trapezoidal method is used.

Secondary

Measure	Time frame	Description
Adverse Events (Part A)	Through part A, from screening day up to 5 to 7 days post final dose, i.e. up to 7 weeks	An AE is any untoward medical occurrence in a study subject which either emerges or worsens from screening, during the clinical study, regardless of its potential relationship to the medicinal product. An AE, therefore, can be any unfavourable or unintended sign, including a clinically-significant abnormal laboratory finding, symptom, or disease temporally associated with the use of a medical product, whether or not it is considered to be study medication related. Data define number of AE reported; frequency for each AE not being reported. Please note: these data in the CSR, as per study crossover design, are provided per sequence and not per intervention. Hence, their representation per intervention it's not applicable.
Subjective Rating of Pain From the ID Capsaicin Model (Part B)	Prior to (within 15 minutes) and at the 15-, 30-, 60-, 90- and 120-minutes post-injection.	Measurement of Pain Score (mm) Over Time. Pain is assessed through a visual analogue scale (VAS) consisting of a 100 mm line, with 0 representing no pain'' and 100 worst pain imaginable. Subjects are asked to mark the VAS using a single vertical stroke at the point they consider to appropriately reflect their level of pain from the injection of capsaicin (not general pain).
Change From Baseline of Pain Score of Hyperalgesia (NRS) by MMRM Analysis.(Part B)	Day 1 at 15, 30, 60, 90 and 120 minutes post injection	Pain reduction/analgesia is measured through visual analogue scale (VAS) consisting of a 100 mm line, with 0 representing no pain'' and 100 worst pain imaginable. Subjects are asked to mark the VAS using a single vertical stroke at the point they consider to appropriately reflect their level of pain from the injection of capsaicin (not general pain). A new VAS are provided for each time-point and subjects are not allowed to see their previous VAS responses. The VAS is scored by measuring from the left-hand end of the scale to the point where the subject has marked the line, and the distance in mm recorded.
Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B)	Prior to (within 15 minutes) and at the 15-, 30-, 60-, 90- and 120-minutes post-injection.	This outcome is assessed by sweeping a standard paintbrush at 1-second intervals across each of the 4 lines intersecting at the injection site drawn onto the skin before the injection. Stimulation begins distal from the injection site and advances in 1 cm increments toward the injection site until a pain response is elicited. Subjects are asked to indicate when the brush first begins to cause any pain or discomfort and the distance of that point from the injection site in centimetres for each line at each time-point is recorded. The area of allodynia was then calculated
Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B)	Prior to (within 15 minutes) and at the 15-, 30-, 60-, 90- and 120-minutes post-injection.	Change from Baseline of Pain in response to brush stimulation of the allodynic area is recorded using an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). The pain score reflects the maximum pain experienced during the assessment.
Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B)	Day 1 Pre-Capsaicin Injection and at 15, 30, 60, 90 and 120 minutes post injection	The AF is determined by tracing the outline of visible skin reddening on to a sheet of acetate placed on the skin using a fine-tipped, permanent marker. The area is subsequently measured using planimetry and the results recorded in the CRF.
Plasma PK Concentrations (Part B)	At Day 1 predose, pre-capsaicin and 2 hours post capsaicin	Plasma concentration levels of ketoprofen and gabapentin in Part B of the study are summarised by timepoint.
Adverse Events (Part B)	The specific period of time over which adverse events data were collected was from screening day up to 5 to 7 days post final dose, i.e. up to 6 weeks for Part B	An AE is any untoward medical occurrence in a study subject which either emerges, or worsens from Screening, during the clinical study, regardless of its potential relationship to the medicinal product. An AE, therefore, can be any unfavourable or unintended sign, including a clinically-significant abnormal laboratory finding, symptom, or disease temporally associated with the use of a medical product, whether or not it is considered to be study medication related. Adverse events may include pre- or post-treatment events that occur as a result of Protocol- mandated procedures (i.e., invasive procedures, modification of subject's previous therapeutic regimen). Data define number of AE reported; frequency for each AE not being reported.

Countries

United Kingdom

Participant flow

Recruitment details

Enrolled is any subject who signed an ICF. Randomized are patients randomly assigned evenly between treatment sequences; Dosed is any subject who actually received at least one dose of IMP during the relevant Part. In part A: n= 6 for all these definitions. In Part B: the enrolled and randomized were n=129; the dosed population is n=128 because 1 pt was randomized to the KLS 40 mg-GABA 17 mg but withdrawn prior to dosing due to a code break issue.

Pre-assignment details

Separate randomization schemes were produced for each Part A (cross-over) of the study and Part B of the study. A simple randomization scheme was used for Part A, while a blocked randomization scheme was used for Part B. Please note: Given the differences between Part A and Part B (design, objectives, endpoints, etc.) study results of the two parts cannot be merged.

Participants by arm

Arm	Count
KLS 80 mg Alone, Then KLS 80 Mg and GABA 34 mg (PART A) KLS-GABA 80 mg-34 mg capsules are administered once in the morning of Day 1 in Part A in Treatment Periods 1 and 2 in the fasted state, according to the randomization schedule. Capsules are administered with 240 mL of water. To maintain the blind, subjects assigned to receive 80 mg-34 mg KLS-GABA also receive a placebo capsule (dummy placebo). KLS 80 mg capsules are administered once in the morning of Day 1 in Part A in Treatment Periods 1 and 2 in the fasted state, according to the randomization schedule. Capsules will be administered with 240 mL of water. Ketoprofen Lysine Salt combined with Gabapentin: KLS-GABA (80 mg-34 mg) in Part A Ketoprofen Lysine Salt: KLS (80 mg) alone in each treatment period in Part A	6
KLS 80 Mg and GABA 34 mg Then KLS 80 mg Alone (PART A) KLS-GABA 80 mg-34 mg capsules are administered once in the morning of Day 1 in Part A in Treatment Periods 1 and 2 in the fasted state, according to the randomization schedule. Capsules are administered with 240 mL of water. To maintain the blind, subjects assigned to receive 80 mg-34 mg KLS-GABA also receive a placebo capsule (dummy placebo). KLS 80 mg capsules are administered once in the morning of Day 1 in Part A in Treatment Periods 1 and 2 in the fasted state, according to the randomization schedule. Capsules will be administered with 240 mL of water. Ketoprofen Lysine Salt combined with Gabapentin: KLS-GABA (80 mg-34 mg) in Part A Ketoprofen Lysine Salt: KLS (80 mg) alone in each treatment period in Part A	6
KLS 40 mg (Part B) In the part B KLS (40 mg, 80 mg or 160 mg) are administered as capsules once in the morning of Day 1 in the fasted state. Capsules are administered with 240 mL of water. To maintain the blind, subjects assigned to receive 160 mg KLS alone are administered two KLS 80 mg capsules and subjects assigned to receive either 40 mg KLS alone or 80 mg KLS alone also receive a placebo capsule (dummy placebo).	16
KLS 80 mg (Part B) In the part B KLS (40 mg, 80 mg or 160 mg) are administered as capsules once in the morning of Day 1 in the fasted state. Capsules are administered with 240 mL of water. To maintain the blind, subjects assigned to receive 160 mg KLS alone are administered two KLS 80 mg capsules and subjects assigned to receive either 40 mg KLS alone or 80 mg KLS alone also receive a placebo capsule (dummy placebo).	16
KLS 160 mg (Part B) In the part B KLS (40 mg, 80 mg or 160 mg) are administered as capsules once in the morning of Day 1 in the fasted state. Capsules are administered with 240 mL of water. To maintain the blind, subjects assigned to receive 160 mg KLS alone are administered two KLS 80 mg capsules and subjects assigned to receive either 40 mg KLS alone or 80 mg KLS alone also receive a placebo capsule (dummy placebo).	16
KLS 40 Mg-GABA 17 mg (Part B) KLS-GABA (40 mg-17mg, 80 mg-34 mg, or 160 mg-68 mg) in Part B are administered as capsules once in the morning of Day 1 in the fasted state. Capsules are administered with 240 mL of water. Subject assigned to receive 40 mg-17 mg KLS-GABA or 80 mg-34 mg KLS-GABA also receive a placebo capsule (dummy placebo).	17
KLS 80 mg- GABA 34 mg (Part B) KLS-GABA (40 mg-17mg, 80 mg-34 mg, or 160 mg-68 mg) in Part B are administered as capsules once in the morning of Day 1 in the fasted state. Capsules are administered with 240 mL of water. Subject assigned to receive 40 mg-17 mg KLS-GABA or 80 mg-34 mg KLS-GABA also receive a placebo capsule (dummy placebo).	16
KLS 160 Mg-GABA 68 mg (Part B) KLS-GABA (40 mg-17mg, 80 mg-34 mg, or 160 mg-68 mg) in Part B are administered as capsules once in the morning of Day 1 in the fasted state. Capsules are administered with 240 mL of water. Subject assigned to receive 40 mg-17 mg KLS-GABA or 80 mg-34 mg KLS-GABA also receive a placebo capsule (dummy placebo).	16
Gabapentin 300 mg (Part B) Gabapentin 300 mg are administered as capsules once in the morning of Day 1 in the fasted state. Capsules are administered with 240 mL of water.To maintain the blind, subjects assigned to receive 300 mg gabapentin also receive a placebo capsule (dummy placebo). Gabapentin: 300 mg	16
Placebo (Part B) To maintain the blind subjects assigned to receive a placebo receive 2 placebo capsules. Capsules will be administered with 240 mL of water. Placebo: 2 capsules to maintain the blind	16
Total	141

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009
Part B	Withdrawal by Subject	0	0	0	0	0	1	0	0	0	0

Baseline characteristics

Characteristic	KLS 80 mg Alone, Then KLS 80 Mg and GABA 34 mg (PART A)	KLS 80 Mg and GABA 34 mg Then KLS 80 mg Alone (PART A)	KLS 40 mg (Part B)	KLS 80 mg (Part B)	KLS 160 mg (Part B)	KLS 40 Mg-GABA 17 mg (Part B)	KLS 80 mg- GABA 34 mg (Part B)	KLS 160 Mg-GABA 68 mg (Part B)	Gabapentin 300 mg (Part B)	Placebo (Part B)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	6 Participants	6 Participants	16 Participants	16 Participants	16 Participants	17 Participants	16 Participants	16 Participants	16 Participants	16 Participants	141 Participants
Age, Continuous	24.5 years STANDARD_DEVIATION 4.93	29.5 years STANDARD_DEVIATION 10.43	29.3 years STANDARD_DEVIATION 8.23	30.8 years STANDARD_DEVIATION 12.86	28.1 years STANDARD_DEVIATION 10.39	29.2 years STANDARD_DEVIATION 8.92	31.1 years STANDARD_DEVIATION 9.68	27.1 years STANDARD_DEVIATION 9.57	27.1 years STANDARD_DEVIATION 10.51	28.9 years STANDARD_DEVIATION 10.01	29.0 years STANDARD_DEVIATION 9.91
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants	5 Participants	15 Participants	16 Participants	15 Participants	17 Participants	16 Participants	14 Participants	15 Participants	16 Participants	133 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	4 Participants
Region of Enrollment United Kingdom	6 participants	6 participants	16 participants	16 participants	16 participants	17 participants	16 participants	16 participants	16 participants	16 participants	141 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	6 Participants	6 Participants	16 Participants	16 Participants	16 Participants	17 Participants	16 Participants	16 Participants	16 Participants	16 Participants	141 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 12	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16
other Total, other adverse events	2 / 12	1 / 12	6 / 16	3 / 16	2 / 16	1 / 16	6 / 16	4 / 16	5 / 16	6 / 16
serious Total, serious adverse events	0 / 12	0 / 12	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16

Outcome results

Primary

Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)

The area of mechanical hyperalgesia was assessed using a standard 24 g von Frey hair. The von Frey hair was applied at 1-second intervals along each of the 4 lines intersecting at the injection site drawn onto the skin before the injection. Stimulation began distal from the injection site and advanced in 1 cm increments toward the injection site until a pain response was elicited. Subjects were asked to report when the von Frey hair first began to cause any pain sensation or discomfort and the distance of that point from the injection site in centimetres for each line at each timepoint was recorded.

Time frame: Day 1 at 15, 30, 60, 90 and 120 minutes post injection

Population: Pharmacodynamic Set: PD Analysis Set consisted of all randomised subjects who received a dose of randomised therapy and were administered the ID capsaicin injection. This population was used for all PD analyses and PD analysis was performed by actual treatment received.

Arm	Measure	Group	Value (MEAN)	Dispersion
KLS 80 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	11.87 cm^2	Standard Error 6.37
KLS 80 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	-0.42 cm^2	Standard Error 6.41
KLS 80 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	1.83 cm^2	Standard Error 6.34
KLS 80 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	12.16 cm^2	Standard Error 6.8
KLS 80 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	13.55 cm^2	Standard Error 6.81
KLS 80 Mg-GABA 34 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	4.12 cm^2	Standard Error 6.81
KLS 80 Mg-GABA 34 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	-6.64 cm^2	Standard Error 6.35
KLS 80 Mg-GABA 34 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	-10.09 cm^2	Standard Error 6.44
KLS 80 Mg-GABA 34 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	7.56 cm^2	Standard Error 6.8
KLS 80 Mg-GABA 34 mg (Part A)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	4.95 cm^2	Standard Error 6.36
KLS 160 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	16.17 cm^2	Standard Error 6.84
KLS 160 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	9.64 cm^2	Standard Error 6.4
KLS 160 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	14.36 cm^2	Standard Error 6.38
KLS 160 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	6.93 cm^2	Standard Error 6.35
KLS 160 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	16.31 cm^2	Standard Error 6.81
KLS 40 Mg-GABA 17 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	12.06 cm^2	Standard Error 6.8
KLS 40 Mg-GABA 17 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	2.57 cm^2	Standard Error 6.41
KLS 40 Mg-GABA 17 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	8.76 cm^2	Standard Error 6.37
KLS 40 Mg-GABA 17 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	14.73 cm^2	Standard Error 6.8
KLS 40 Mg-GABA 17 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	7.38 cm^2	Standard Error 6.35
KLS 80 mg- GABA 34 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	12.89 cm^2	Standard Error 6.8
KLS 80 mg- GABA 34 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	23.15 cm^2	Standard Error 6.37
KLS 80 mg- GABA 34 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	17.02 cm^2	Standard Error 6.82
KLS 80 mg- GABA 34 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	7.23 cm^2	Standard Error 6.34
KLS 80 mg- GABA 34 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	2.40 cm^2	Standard Error 6.41
KLS 160 Mg-GABA 68 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	-2.49 cm^2	Standard Error 6.8
KLS 160 Mg-GABA 68 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	-4.23 cm^2	Standard Error 6.35
KLS 160 Mg-GABA 68 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	5.69 cm^2	Standard Error 6.8
KLS 160 Mg-GABA 68 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	5.41 cm^2	Standard Error 6.36
KLS 160 Mg-GABA 68 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	-10.89 cm^2	Standard Error 6.42
Gabapentin 300 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	6.28 cm^2	Standard Error 6.8
Gabapentin 300 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	12.28 cm^2	Standard Error 6.37
Gabapentin 300 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	15.67 cm^2	Standard Error 6.81
Gabapentin 300 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	-8.22 cm^2	Standard Error 6.44
Gabapentin 300 mg (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	0.32 cm^2	Standard Error 6.35
Placebo (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 120 minutes post injection.The mean is an adjusted mean.	-6.43 cm^2	Standard Error 6.4
Placebo (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 90 minutes post injection.The mean is an adjusted mean.	-0.51 cm^2	Standard Error 6.35
Placebo (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 15 minutes post injection. The mean is an adjusted mean	11.85 cm^2	Standard Error 6.36
Placebo (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 60 minutes post injection.The mean is an adjusted mean.	0.18 cm^2	Standard Error 6.81
Placebo (Part B)	Change From Baseline in Area of Hyperalgesia (cm^2) Post-capsaicin Injection by MMRM Analysis. (Part B)	at 30 minutes post injection.The mean is an adjusted mean	1.45 cm^2	Standard Error 6.82

Comparison: Outcome Measure at 15 minutes post injectionp-value: 0.99895% CI: [-17.81, 17.86]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 15 minutes post injectionp-value: 0.44595% CI: [-24.73, 10.93]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 15 minutes post injectionp-value: 0.78195% CI: [-15.33, 20.36]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 15 minutes post injectionp-value: 0.73295% CI: [-20.93, 14.75]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 15 minutes post injectionp-value: 0.21295% CI: [-6.53, 29.14]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 15 minutes post injectionp-value: 0.47695% CI: [-24.27, 11.39]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 15 minutes post injectionp-value: 0.96295% CI: [-17.4, 18.26]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 30 minutes post injectionp-value: 0.21195% CI: [-6.96, 31.16]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 30 minutes post injectionp-value: 0.78295% CI: [-16.4, 21.73]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 30 minutes post injectionp-value: 0.12995% CI: [-4.34, 33.78]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 30 minutes post injectionp-value: 0.17195% CI: [-5.8, 32.35]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 30 minutes post injectionp-value: 0.10895% CI: [-3.49, 34.62]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 30 minutes post injectionp-value: 0.66195% CI: [-14.83, 23.3]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 30 minutes post injectionp-value: 0.14295% CI: [-4.85, 33.27]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 60 minutes post injectionp-value: 0.21695% CI: [-7.08, 31.04]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 60 minutes post injectionp-value: 0.44595% CI: [-11.71, 26.48]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 60 minutes post injectionp-value: 0.09695% CI: [-2.92, 35.19]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 60 minutes post injectionp-value: 0.2295% CI: [-7.19, 30.96]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 60 minutes post injectionp-value: 0.18995% CI: [-6.35, 31.78]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 60 minutes post injectionp-value: 0.78295% CI: [-21.75, 16.41]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 60 minutes post injectionp-value: 0.52895% CI: [-12.98, 25.18]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 90 minutes post injectionp-value: 0.79595% CI: [-15.45, 20.12]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 90 minutes post injectionp-value: 0.49795% CI: [-23.96, 11.69]mean difference

Comparison: Outcome Measure at 90 minutes post injectionp-value: 0.40995% CI: [-10.34, 25.21]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 90 minutes post injectionp-value: 0.38295% CI: [-9.92, 25.7]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 90 minutes post injectionp-value: 0.3995% CI: [-10.05, 25.54]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 90 minutes post injectionp-value: 0.6895% CI: [-21.54, 14.1]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 90 minutes post injectionp-value: 0.92795% CI: [-16.99, 18.65]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 120 minutes post injectionp-value: 0.50895% CI: [-11.95, 23.98]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 120 minutes post injectionp-value: 0.68895% CI: [-21.66, 14.35]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 120 minutes post injectionp-value: 0.07995% CI: [-1.88, 34.03]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 120 minutes post injectionp-value: 0.32395% CI: [-8.96, 26.96]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 120 minutes post injectionp-value: 0.18395% CI: [-5.39, 27.85]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 120 minutes post injectionp-value: 0.75695% CI: [-19.24, 14.02]Mixed Model Repeated Measures.

Comparison: Outcome Measure at 120 minutes post injectionp-value: 0.63895% CI: [-12.68, 20.59]Mixed Model Repeated Measures.

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),

PK parameters of ketoprofen when administered alone and when administered in combination with gabapentin in healthy male subjects were assessed. Outcome measure at 0h,16h,24h,36h, and 48h postdose below limit of quantification (0.04 μg/mL). The area under the concentration versus time curve from time zero to the last quantifiable concentration (C-last), calculated by the linear up-log down trapezoidal method; i.e. when concentrations are increasing (as in the absorption phase), the linear trapezoidal method is used, when concentrations are decreasing (as in the elimination phase), the logarithmic trapezoidal method is used.