A Study on Ketoprofen Lysine Salt (KLS) + Gabapentin (GABA) vs KLS to Investigate Their Pharmacodynamic in Healthy Males
Condition: No Condition
Study type: Interventional
Phase: Phase 1

Summary: 
      Part A The primary objective of this study is to determine the single dose pharmacokinetics
      (PK) of ketoprofen lysine salt combined with gabapentin (KLS-GABA [80 mg-34 mg]) compared to
      KLS alone (80 mg) in healthy male subjects.

      The secondary objective of this study is:

      • To determine the safety and tolerability of a single oral dose of KLS-GABA (80 mg-34 mg)
      compared to KLS alone (80 mg) in healthy male subjects.

      Part B The primary objective of this study is to determine the pharmacodynamic (PD) effects
      of KLS-GABA in the Intradermal (ID) capsaicin model in healthy male subjects.

      The secondary objectives of this study are:

        -  To further investigate the safety, tolerability, and PK of single oral doses of KLS-GABA
           and KLS alone.

        -  To investigate the possible relationship between plasma levels of drug and efficacy in
           pain reduction.
    

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

Intervention name(s): Ketoprofen Lysine Salt combined with Gabapentin; Ketoprofen Lysine Salt; Gabapentin; Placebo
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): KLS-GABA (80 mg-34 mg) in Part A and KLS-GABA (40 mg-17 mg or 80 mg-34 mg or 160 mg-68 mg) in Part B; KLS (80 mg) alone in each treatment period in Part A and KLS alone (40 mg, 80 mg, or 160 mg) in Part B; 300 mg; 2 capsules to maintain the blind
Other intervention name(s): KLS-GABA; KLS; GABA
Intervention MeSH terms: Ketoprofen; Ketoprofen lysine; Gabapentin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: In the Part B of the study the Intradermal (ID) Capsaicin Model is used.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Male healthy volunteers