Two-way Crossover, Single Dose Randomized, Two-stage Bioequivalence of Ketoprofen Lysine Salt Immediate Release vs Granules Oral Solution
Condition: Pain Disorders
MeSH terms: Somatoform Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The present bioequivalence phase I study is needed to compare the bioavailability and the
      concentration-time profile of the new immediate release formulation of KLS 40 mg with the
      reference compound OKi®, ketoprofen lysine salt 80 mg granules for oral solution (bipartite
      sachets).

      The objective of the study is to investigate the bioequivalence between two formulations
      containing ketoprofen lysine salt (KLS) when administered as single oral dose in two
      consecutive study periods to healthy male and female volunteers under fasting conditions.
    

Detailed description: 
      As a part of the Dompé extension line program, Dompé develops a new immediate release tablets
      formulation of ketoprofen lysine salt 40 mg.

      The new immediate release tablets formulation of KLS 40 mg (corresponding to 25 mg of
      ketoprofen free acid) is expected to be essentially similar to the formulations of ketoprofen
      25 mg for oral administration, that are already available in the European Community with the
      same indications: pain such as episodic tension-type headache, dental pain, neuralgia,
      dysmenorrhoea, postpartum pain, muscular and osteoarticular pain.

      The objective of the study is to investigate the bioequivalence (Cmax and extent of
      absorption of ketoprofen after single dose administration)between two formulations containing
      ketoprofen lysine salt (KLS) when administered as single oral dose in two consecutive study
      periods to healthy male and female volunteers under fasting conditions. Furthermore, to
      collect safety and tolerability data after single dose administration of test and reference.

      Due to the lack of information about the PK profile of the new formulation it was not
      possible to calculate the sample size properly.

      For this reason it was decided to use a "two stage" bioequivalence study design. The sample
      size of 30 subjects is regarded as sufficient to satisfy the primary objective for the first
      stage of the study.

      After the end of study stage 1, PK parameters will be calculated and an ad interim
      bioequivalence test will be performed on the calculated PK parameters Cmax, AUC0-t and
      AUC0-∞. To safeguard the overall type I error, the Pocock spending function will be used to
      determine the α level of the bioequivalence test. Should bioequivalence be proven with the
      results of the subjects of the first stage and with an a posteriori calculated power of at
      least 80%, the primary objective of the study would then be satisfied and the second study
      stage will not take place. Should bioequivalence not be proven with the results of the
      subjects of the first stage or should it be proven with an a posteriori calculated power
      lower than 80%, the overall sample size for the study (stage 1 plus 2) will be calculated on
      the basis of the ad interim bioequivalence results. The Sponsor will decide whether the study
      has to continue or not. In the first case, the additional subjects will be enrolled into the
      second study stage. After completion of stage 2, the PK analysis and the bioequivalence test
      will be performed on the pooled subjects of the two study stages. The second stage will be
      performed after notification of the sample size to the local Ethics Committee and to the
      central Swiss authority (Swissmedic).

      An open design was chosen as it was considered adequate to evaluate objective measures such
      as pharmacokinetic parameters. All the personnel involved in the analytical determinations of
      the ketoprofen in the plasma samples withdrawn from the volunteers will be maintained in
      blinding.

      The sequence of treatments in the two study periods will be assigned to each randomised
      subject according to a computer generated randomisation list.

      A wash-out period of at least 4 days between the two administrations is justified by the
      elimination half-life of the ketoprofen (1-2 h).
    

Intervention name(s): KSL 40 mg; OKi® 80 mg
Intervention type(s): Drug; Drug
Intervention description(s): Ketoprofen lysine salt oral immediate release tablets 40 mg; Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: headache; dental pain; neuralgia; dysmenorrhoea; muscular and osteoarticular pain