Trial Outcomes & Findings for A Study on Ketoprofen Lysine Salt (KLS) + Gabapentin (GABA) vs KLS to Investigate Their Pharmacodynamic in Healthy Males (NCT NCT04802967)

Last Updated: 2024-12-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

141 participants

Primary outcome timeframe

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Results posted on

2024-12-27

Participant Flow

"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and randomized were n=129; the dosed population is n=128 because 1 pt was randomized to the KLS 40 mg-GABA 17 mg but withdrawn prior to dosing due to a code break issue.

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.

Participant milestones

Participant milestones
Measure	"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	"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	KLS 40 mg 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).	KLS 80 mg 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).	KLS 160 mg 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).	KLS 40 Mg-GABA 17 mg 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).	KLS 80 mg- GABA 34 mg 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).	KLS 160 Mg-GABA 68 mg 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).	Gabapentin 300 mg 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).	Placebo 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
Part A STARTED	6	6	0	0	0	0	0	0	0	0
Part A Enrolled, Randomized and Dosed	6	6	0	0	0	0	0	0	0	0
Part A COMPLETED	6	6	0	0	0	0	0	0	0	0
Part A NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Part B STARTED	0	0	16	16	16	17	16	16	16	16
Part B Enrolled, Randomized and Dosed	0	0	16	16	16	16	16	16	16	16
Part B COMPLETED	0	0	16	16	16	16	16	16	16	16
Part B NOT COMPLETED	0	0	0	0	0	1	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	"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	"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	KLS 40 mg 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).	KLS 80 mg 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).	KLS 160 mg 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).	KLS 40 Mg-GABA 17 mg 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).	KLS 80 mg- GABA 34 mg 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).	KLS 160 Mg-GABA 68 mg 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).	Gabapentin 300 mg 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).	Placebo 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
Part B Withdrawal by Subject	0	0	0	0	0	1	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	"KLS 80 mg Alone, Then KLS 80 Mg and GABA 34 mg" (PART A) n=6 Participants 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	"KLS 80 Mg and GABA 34 mg Then KLS 80 mg Alone" (PART A) n=6 Participants 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	KLS 40 mg (Part B) n=16 Participants 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).	KLS 80 mg (Part B) n=16 Participants 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).	KLS 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=17 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	Placebo (Part B) n=16 Participants 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	Total n=141 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants	16 Participants n=4 Participants	16 Participants n=21 Participants	17 Participants n=8 Participants	16 Participants n=8 Participants	16 Participants n=24 Participants	16 Participants n=42 Participants	16 Participants n=42 Participants	141 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Continuous	24.5 years STANDARD_DEVIATION 4.93 • n=5 Participants	29.5 years STANDARD_DEVIATION 10.43 • n=7 Participants	29.3 years STANDARD_DEVIATION 8.23 • n=5 Participants	30.8 years STANDARD_DEVIATION 12.86 • n=4 Participants	28.1 years STANDARD_DEVIATION 10.39 • n=21 Participants	29.2 years STANDARD_DEVIATION 8.92 • n=8 Participants	31.1 years STANDARD_DEVIATION 9.68 • n=8 Participants	27.1 years STANDARD_DEVIATION 9.57 • n=24 Participants	27.1 years STANDARD_DEVIATION 10.51 • n=42 Participants	28.9 years STANDARD_DEVIATION 10.01 • n=42 Participants	29.0 years STANDARD_DEVIATION 9.91 • n=42 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants	16 Participants n=4 Participants	16 Participants n=21 Participants	17 Participants n=8 Participants	16 Participants n=8 Participants	16 Participants n=24 Participants	16 Participants n=42 Participants	16 Participants n=42 Participants	141 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants	16 Participants n=4 Participants	15 Participants n=21 Participants	17 Participants n=8 Participants	16 Participants n=8 Participants	14 Participants n=24 Participants	15 Participants n=42 Participants	16 Participants n=42 Participants	133 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants	6 participants n=7 Participants	16 participants n=5 Participants	16 participants n=4 Participants	16 participants n=21 Participants	17 participants n=8 Participants	16 participants n=8 Participants	16 participants n=24 Participants	16 participants n=42 Participants	16 participants n=42 Participants	141 participants n=42 Participants

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=12 Participants 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 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).	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).	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).	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).	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	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
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 μg*h/mL Standard Deviation 2.70	11.1 μg*h/mL Standard Deviation 2.94	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=12 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A):AUC From Zero to 12 Hours Postdose (AUC0-12h)	10.3 μg*h/mL Standard Deviation 2.25	11.0 μg*h/mL Standard Deviation 2.89	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=12 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to 24 Hours Postdose (AUC0-24h)	10.5 μg*h/mL Standard Deviation 2.42	11.2 μg*h/mL Standard Deviation 3.02	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=12 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A):AUC From Zero to 36 Hours Postdose (AUC0-36h)	10.5 μg*h/mL Standard Deviation 2.56	11.2 μg*h/mL Standard Deviation 3.00	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=12 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to 48 Hours Postdose (AUC0-48h)	10.6 μg*h/mL Standard Deviation 2.67	11.3 μg*h/mL Standard Deviation 2.99	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=12 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Maximum Plasma Concentration (Cmax)	6.69 μg/mL Standard Deviation 1.88	7.97 μg/mL Standard Deviation 2.19	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=12 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Time to Maximum Plasma Concentration (Tmax)	0.501 h Standard Deviation 0.00481	0.542 h Standard Deviation 0.144	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=10 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): Half-life (t1/2)	3.77 h Standard Deviation 6.56	2.88 h Standard Deviation 1.40	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=16 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=16 Participants 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 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=16 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	Placebo (Part B) n=16 Participants 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
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	4.95 cm^2 Standard Error 6.36	14.36 cm^2 Standard Error 6.38	8.76 cm^2 Standard Error 6.37	23.15 cm^2 Standard Error 6.37	5.41 cm^2 Standard Error 6.36	12.28 cm^2 Standard Error 6.37	11.85 cm^2 Standard Error 6.36
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	4.12 cm^2 Standard Error 6.81	16.17 cm^2 Standard Error 6.84	14.73 cm^2 Standard Error 6.80	17.02 cm^2 Standard Error 6.82	5.69 cm^2 Standard Error 6.80	15.67 cm^2 Standard Error 6.81	1.45 cm^2 Standard Error 6.82
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 6.80	7.56 cm^2 Standard Error 6.80	16.31 cm^2 Standard Error 6.81	12.06 cm^2 Standard Error 6.80	12.89 cm^2 Standard Error 6.80	-2.49 cm^2 Standard Error 6.80	6.28 cm^2 Standard Error 6.80	0.18 cm^2 Standard Error 6.81
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	-6.64 cm^2 Standard Error 6.35	6.93 cm^2 Standard Error 6.35	7.38 cm^2 Standard Error 6.35	7.23 cm^2 Standard Error 6.34	-4.23 cm^2 Standard Error 6.35	0.32 cm^2 Standard Error 6.35	-0.51 cm^2 Standard Error 6.35
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	-10.09 cm^2 Standard Error 6.44	9.64 cm^2 Standard Error 6.40	2.57 cm^2 Standard Error 6.41	2.40 cm^2 Standard Error 6.41	-10.89 cm^2 Standard Error 6.42	-8.22 cm^2 Standard Error 6.44	-6.43 cm^2 Standard Error 6.40

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data.

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%.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=12 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=10 Participants 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 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).	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).	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).	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).	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	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
Plasma PK Concentrations and Parameters of Ketoprofen (Part A): AUC From Zero to Infinity (AUC0-∞),	10.7 μg*h/mL Standard Deviation 2.96	11.4 μg*h/mL Standard Deviation 3.06	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Through part A, from screening day up to 5 to 7 days post final dose, i.e. up to 7 weeks

Population: Safety Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS).

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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=6 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=6 Participants 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 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).	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).	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).	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).	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	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
Adverse Events (Part A) TEAE: Definitely Related to Treatment	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) Overall TEAE	2 Number of events	1 Number of events	—	—	—	—	—	—
Adverse Events (Part A) Serious treatment-emergent adverse event	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) TEAE Leading to Discontinuation	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) TEAE leading to Death	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) Treatment-emergent adverse event: Mild Severity	2 Number of events	1 Number of events	—	—	—	—	—	—
Adverse Events (Part A) Treatment-emergent adverse event: Moderate Severity	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) Treatment-emergent adverse event: Severe Severity	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) TEAE: Not Related to Treatment	2 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) TEAE: Unlikely Related to Treatment	0 Number of events	1 Number of events	—	—	—	—	—	—
Adverse Events (Part A) TEAE: Possibly Related to Treatment	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) TEAE: Probably Related to Treatment	0 Number of events	0 Number of events	—	—	—	—	—	—
Adverse Events (Part A) TEAE: Related to Treatment	0 Number of events	0 Number of events	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=16 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=16 Participants 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 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=16 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	Placebo (Part B) n=16 Participants 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
Subjective Rating of Pain From the ID Capsaicin Model (Part B) 120 Minutes Post Injection	1.38 score on a scale Standard Deviation 2.446	1.75 score on a scale Standard Deviation 2.436	1.25 score on a scale Standard Deviation 1.807	1.88 score on a scale Standard Deviation 2.156	1.50 score on a scale Standard Deviation 2.422	1.00 score on a scale Standard Deviation 0.966	1.50 score on a scale Standard Deviation 4.163	0.44 score on a scale Standard Deviation 0.814
Subjective Rating of Pain From the ID Capsaicin Model (Part B) Pre-Capsaicin Injection	0.44 score on a scale Standard Deviation 1.365	0.88 score on a scale Standard Deviation 2.125	0.69 score on a scale Standard Deviation 2.056	0.88 score on a scale Standard Deviation 2.918	0.06 score on a scale Standard Deviation 3.296	0.00 score on a scale Standard Deviation 3.055	0.44 score on a scale Standard Deviation 0.892	0.56 score on a scale Standard Deviation 3.425
Subjective Rating of Pain From the ID Capsaicin Model (Part B) 15 Minutes Post Injection	-2.56 score on a scale Standard Deviation 15.849	3.25 score on a scale Standard Deviation 19.182	-5.13 score on a scale Standard Deviation 12.638	3.63 score on a scale Standard Deviation 15.949	-1.50 score on a scale Standard Deviation 14.320	-3.75 score on a scale Standard Deviation 15.813	-2.94 score on a scale Standard Deviation 13.542	-6.81 score on a scale Standard Deviation 11.862
Subjective Rating of Pain From the ID Capsaicin Model (Part B) 30 Minutes Post Injection	21.94 score on a scale Standard Deviation 17.789	30.50 score on a scale Standard Deviation 21.891	29.38 score on a scale Standard Deviation 18.846	27.19 score on a scale Standard Deviation 17.848	23.13 score on a scale Standard Deviation 17.393	24.44 score on a scale Standard Deviation 15.349	29.44 score on a scale Standard Deviation 20.324	15.50 score on a scale Standard Deviation 13.866
Subjective Rating of Pain From the ID Capsaicin Model (Part B) 60 Minutes Post Injection	10.38 score on a scale Standard Deviation 9.351	15.06 score on a scale Standard Deviation 13.897	8.88 score on a scale Standard Deviation 7.338	10.88 score on a scale Standard Deviation 10.424	10.56 score on a scale Standard Deviation 13.171	8.88 score on a scale Standard Deviation 11.039	8.56 score on a scale Standard Deviation 9.598	5.25 score on a scale Standard Deviation 8.323
Subjective Rating of Pain From the ID Capsaicin Model (Part B) 90 Minutes Post Injection	2.75 score on a scale Standard Deviation 3.624	3.13 score on a scale Standard Deviation 4.801	2.56 score on a scale Standard Deviation 4.427	3.31 score on a scale Standard Deviation 3.911	3.69 score on a scale Standard Deviation 5.930	2.25 score on a scale Standard Deviation 3.066	2.81 score on a scale Standard Deviation 5.431	1.50 score on a scale Standard Deviation 2.683

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=16 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=16 Participants 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 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=16 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	Placebo (Part B) n=16 Participants 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
Change From Baseline of Pain Score of Hyperalgesia (NRS) by MMRM Analysis.(Part B) 15 Minutes Post Injection	0.10 units on a scale Standard Error 0.37	0.94 units on a scale Standard Error 0.37	0.46 units on a scale Standard Error 0.37	0.81 units on a scale Standard Error 0.37	0.75 units on a scale Standard Error 0.37	0.79 units on a scale Standard Error 0.37	0.80 units on a scale Standard Error 0.37	0.01 units on a scale Standard Error 0.37
Change From Baseline of Pain Score of Hyperalgesia (NRS) by MMRM Analysis.(Part B) 90 Minutes Post Injection	-0.68 units on a scale Standard Error 0.31	-0.56 units on a scale Standard Error 0.31	-0.25 units on a scale Standard Error 0.31	-0.54 units on a scale Standard Error 0.31	-0.24 units on a scale Standard Error 0.31	-0.37 units on a scale Standard Error 0.31	-0.23 units on a scale Standard Error 0.31	-0.88 units on a scale Standard Error 0.31
Change From Baseline of Pain Score of Hyperalgesia (NRS) by MMRM Analysis.(Part B) 120 Minutes Post Injection	-0.58 units on a scale Standard Error 0.30	-0.79 units on a scale Standard Error 0.30	-0.65 units on a scale Standard Error 0.30	-0.59 units on a scale Standard Error 0.30	-0.70 units on a scale Standard Error 0.30	-0.33 units on a scale Standard Error 0.30	-0.52 units on a scale Standard Error 0.30	-0.92 units on a scale Standard Error 0.30
Change From Baseline of Pain Score of Hyperalgesia (NRS) by MMRM Analysis.(Part B) 30 Minutes Post Injection	0.05 units on a scale Standard Error 0.38	0.58 units on a scale Standard Error 0.39	0.30 units on a scale Standard Error 0.38	0.06 units on a scale Standard Error 0.39	0.47 units on a scale Standard Error 0.39	0.39 units on a scale Standard Error 0.38	0.46 units on a scale Standard Error 0.39	-0.51 units on a scale Standard Error 0.38
Change From Baseline of Pain Score of Hyperalgesia (NRS) by MMRM Analysis.(Part B) 60 Minutes Post Injection	-0.67 units on a scale Standard Error 0.32	0.00 units on a scale Standard Error 0.32	-0.30 units on a scale Standard Error 0.32	-0.50 units on a scale Standard Error 0.32	0.02 units on a scale Standard Error 0.32	-0.18 units on a scale Standard Error 0.32	-0.08 units on a scale Standard Error 0.32	-0.49 units on a scale Standard Error 0.32

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=16 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=16 Participants 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 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=16 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	Placebo (Part B) n=16 Participants 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
Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 30 Minutes Post Injection	1.904 cm^2 Standard Deviation 29.8020	-6.738 cm^2 Standard Deviation 20.1917	8.259 cm^2 Standard Deviation 22.2606	9.301 cm^2 Standard Deviation 28.4396	3.955 cm^2 Standard Deviation 28.6202	-1.524 cm^2 Standard Deviation 26.5909	-4.178 cm^2 Standard Deviation 23.6343	-5.425 cm^2 Standard Deviation 34.2194
Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 60 Minutes Post Injection	4.176 cm^2 Standard Deviation 17.0876	-5.060 cm^2 Standard Deviation 19.2494	5.878 cm^2 Standard Deviation 11.6536	8.264 cm^2 Standard Deviation 22.6764	-2.630 cm^2 Standard Deviation 10.5206	-6.056 cm^2 Standard Deviation 20.7553	-11.710 cm^2 Standard Deviation 21.6124	-4.641 cm^2 Standard Deviation 19.9627
Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 90 Minutes Post Injection	5.238 cm^2 Standard Deviation 12.8091	-1.791 cm^2 Standard Deviation 9.5419	4.841 cm^2 Standard Deviation 10.5503	3.646 cm^2 Standard Deviation 17.8697	-1.104 cm^2 Standard Deviation 12.9476	-2.719 cm^2 Standard Deviation 16.2512	3.846 cm^2 Standard Deviation 16.6439	-2.526 cm^2 Standard Deviation 11.6839
Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) Pre-Capsaicin Injection	0.000 cm^2 Standard Deviation 0.000	0.000 cm^2 Standard Deviation 0.000	0.000 cm^2 Standard Deviation 0.000	0.000 cm^2 Standard Deviation 0.000	0.000 cm^2 Standard Deviation 0.000	0.000 cm^2 Standard Deviation 0.000	0.000 cm^2 Standard Deviation 0.000	0.000 cm^2 Standard Deviation 0.000
Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 15 Minutes Post Injection	4.574 cm^2 Standard Deviation 23.6690	1.769 cm^2 Standard Deviation 22.2854	4.087 cm^2 Standard Deviation 26.5438	11.246 cm^2 Standard Deviation 21.8903	0.375 cm^2 Standard Deviation 31.3485	-4.861 cm^2 Standard Deviation 24.1747	-4.083 cm^2 Standard Deviation 23.4260	2.011 cm^2 Standard Deviation 28.6385
Change From Baseline of Area of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 120 Minutes Post Injection	0.641 cm^2 Standard Deviation 6.3370	-4.752 cm^2 Standard Deviation 12.7411	3.206 cm^2 Standard Deviation 9.2605	5.978 cm^2 Standard Deviation 24.1098	-0.813 cm^2 Standard Deviation 14.1667	-0.596 cm^2 Standard Deviation 6.5890	-0.023 cm^2 Standard Deviation 9.2870	-5.349 cm^2 Standard Deviation 11.4016

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=16 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=16 Participants 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 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=16 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	Placebo (Part B) n=16 Participants 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
Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) Pre-Capsaicin Injection	0.06 score on a scale Standard Deviation 0.250	0.00 score on a scale Standard Deviation 0.365	0.00 score on a scale Standard Deviation 0.000	0.00 score on a scale Standard Deviation 0.000	-0.13 score on a scale Standard Deviation 0.500	-0.06 score on a scale Standard Deviation 0.250	0.00 score on a scale Standard Deviation 0.000	0.00 score on a scale Standard Deviation 0.000
Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 15 Minutes Post Injection	-0.63 score on a scale Standard Deviation 0.806	0.19 score on a scale Standard Deviation 1.905	-0.38 score on a scale Standard Deviation 1.147	0.19 score on a scale Standard Deviation 1.223	-0.50 score on a scale Standard Deviation 1.033	-0.25 score on a scale Standard Deviation 1.342	-0.13 score on a scale Standard Deviation 0.885	-0.56 score on a scale Standard Deviation 1.590
Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 30 Minutes Post Injection	-0.19 score on a scale Standard Deviation 0.981	-0.19 score on a scale Standard Deviation 1.276	-0.50 score on a scale Standard Deviation 0.966	0.31 score on a scale Standard Deviation 0.946	0.00 score on a scale Standard Deviation 1.033	-0.38 score on a scale Standard Deviation 1.784	-0.06 score on a scale Standard Deviation 0.854	-0.56 score on a scale Standard Deviation 1.413
Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 60 Minutes Post Injection	-0.38 score on a scale Standard Deviation 0.885	-0.19 score on a scale Standard Deviation 1.109	-0.13 score on a scale Standard Deviation 0.719	0.25 score on a scale Standard Deviation 1.438	0.06 score on a scale Standard Deviation 1.289	-0.44 score on a scale Standard Deviation 1.263	-0.50 score on a scale Standard Deviation 1.366	-0.19 score on a scale Standard Deviation 1.047
Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 90 Minutes Post Injection	-0.31 score on a scale Standard Deviation 0.704	0.00 score on a scale Standard Deviation 0.730	0.13 score on a scale Standard Deviation 0.500	0.00 score on a scale Standard Deviation 1.095	-0.31 score on a scale Standard Deviation 1.078	-0.38 score on a scale Standard Deviation 1.258	-0.63 score on a scale Standard Deviation 1.708	-0.19 score on a scale Standard Deviation 1.047
Change From Baseline in Pain Score of Brush-evoked Allodynia From the ID Capsaicin Model (Part B) 120 Minutes Post Injection	-0.06 score on a scale Standard Deviation 0.443	0.13 score on a scale Standard Deviation 0.619	0.06 score on a scale Standard Deviation 0.574	-0.25 score on a scale Standard Deviation 0.856	-0.31 score on a scale Standard Deviation 1.138	-0.06 score on a scale Standard Deviation 1.063	-0.56 score on a scale Standard Deviation 1.263	-0.31 score on a scale Standard Deviation 0.793

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=16 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=16 Participants 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 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=16 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	Placebo (Part B) n=16 Participants 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
Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B) 15 Minutes Post Injection	3.77 cm2 Standard Deviation 21.565	6.27 cm2 Standard Deviation 11.905	9.19 cm2 Standard Deviation 13.719	6.33 cm2 Standard Deviation 17.756	10.09 cm2 Standard Deviation 25.933	6.16 cm2 Standard Deviation 12.363	6.86 cm2 Standard Deviation 20.153	8.44 cm2 Standard Deviation 16.814
Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B) 30 Minutes Post Injection	6.58 cm2 Standard Deviation 20.856	7.36 cm2 Standard Deviation 8.660	7.14 cm2 Standard Deviation 12.503	5.24 cm2 Standard Deviation 16.808	15.33 cm2 Standard Deviation 14.637	10.82 cm2 Standard Deviation 14.225	7.48 cm2 Standard Deviation 14.857	6.63 cm2 Standard Deviation 15.525
Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B) 90 Minutes Post Injection	0.73 cm2 Standard Deviation 1.360	3.34 cm2 Standard Deviation 8.184	-0.34 cm2 Standard Deviation 2.138	0.78 cm2 Standard Deviation 1.596	0.41 cm2 Standard Deviation 2.573	0.02 cm2 Standard Deviation 0.813	-0.71 cm2 Standard Deviation 3.328	1.48 cm2 Standard Deviation 3.694
Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B) 120 Minutes Post Injection	-0.06 cm2 Standard Deviation 0.675	0.19 cm2 Standard Deviation 0.512	0.14 cm2 Standard Deviation 0.961	0.20 cm2 Standard Deviation 1.191	0.17 cm2 Standard Deviation 0.910	0.26 cm2 Standard Deviation 0.530	0.09 cm2 Standard Deviation 0.558	0.18 cm2 Standard Deviation 0.872
Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B) Pre-Capsaicin Injection	0.00 cm2 Standard Deviation 0.00	0.00 cm2 Standard Deviation 0.00	0.00 cm2 Standard Deviation 0.00	0.00 cm2 Standard Deviation 0.00	0.00 cm2 Standard Deviation 0.00	0.00 cm2 Standard Deviation 0.00	0.00 cm2 Standard Deviation 0.00	0.00 cm2 Standard Deviation 0.00
Change From Baseline in Area of Flare (AF) From the ID Capsaicin Model (Part B) 60 Minutes Post Injection	6.07 cm2 Standard Deviation 10.843	4.58 cm2 Standard Deviation 12.976	5.12 cm2 Standard Deviation 17.524	8.14 cm2 Standard Deviation 8.159	8.89 cm2 Standard Deviation 10.602	5.96 cm2 Standard Deviation 11.399	7.88 cm2 Standard Deviation 12.083	2.39 cm2 Standard Deviation 14.813

SECONDARY outcome

Timeframe: At Day 1 predose, pre-capsaicin and 2 hours post capsaicin

Population: PK Analysis Set: consisted of all subjects who received a dose of the IMP (KLS-GABA or KLS) and had evaluable PK data. Data were below limit of quantification (Not Evaluable) for all the 000 data presented in the table.

Plasma concentration levels of ketoprofen and gabapentin in Part B of the study are summarised by timepoint.

Outcome measures

Outcome measures
Measure	KLS 80 mg (Part A) n=16 Participants 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.	KLS 80 Mg-GABA 34 mg (Part A) n=16 Participants 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 160 mg (Part B) n=16 Participants 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).	KLS 40 Mg-GABA 17 mg (Part B) n=16 Participants 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).	KLS 80 mg- GABA 34 mg (Part B) n=16 Participants 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).	KLS 160 Mg-GABA 68 mg (Part B) n=16 Participants 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).	Gabapentin 300 mg (Part B) n=16 Participants 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	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
Plasma PK Concentrations (Part B) Gabapentin Concentration: Pre Capsaicin Injection	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	0.189 ug/mL Standard Deviation 0.0815	0.321 ug/mL Standard Deviation 0.1370	0.693 ug/mL Standard Deviation 0.2455	1.375 ug/mL Standard Deviation 0.5394	—
Plasma PK Concentrations (Part B) Gabapentin Concentration: 2h Post Injection	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	0.182 ug/mL Standard Deviation 0.0312	0.320 ug/mL Standard Deviation 0.0714	0.675 ug/mL Standard Deviation 0.1572	2.241 ug/mL Standard Deviation 0.7926	—
Plasma PK Concentrations (Part B) Ketoprofen Concentration: Pre Capsaicin Injection	2.224 ug/mL Standard Deviation 0.6594	5.278 ug/mL Standard Deviation 1.0825	10.748 ug/mL Standard Deviation 2.6576	2.526 ug/mL Standard Deviation 0.5912	5.024 ug/mL Standard Deviation 1.0030	11.259 ug/mL Standard Deviation 2.6875	000 ug/mL Standard Deviation 000	—
Plasma PK Concentrations (Part B) Ketoprofen Concentration: 2h Post Injection	0.456 ug/mL Standard Deviation 0.1582	1.056 ug/mL Standard Deviation 0.3847	2.106 ug/mL Standard Deviation 0.6011	0.473 ug/mL Standard Deviation 0.1487	1.036 ug/mL Standard Deviation 0.4056	2.267 ug/mL Standard Deviation 0.7075	000 ug/mL Standard Deviation 000	—
Plasma PK Concentrations (Part B) Gabapentin Concentration: Pre Dose	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	—
Plasma PK Concentrations (Part B) Ketoprofen Concentration: Pre Dose	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	000 ug/mL Standard Deviation 000	—

SECONDARY outcome

Timeframe: 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

Population: Safety Analysis Set consisted of all subjects who received a dose of the IMP (KLS, KLS-GABA, gabapentin, or placebo). Safety data were presented by actual treatment received.

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.