Study Evaluating Efficacy and Safety of OSU6162 in the Treatment of Residual Symptoms After Stroke
Condition: Stroke Sequelae
MeSH terms: Stroke
Study type: Interventional
Phase: Phase 2

Summary: 
      Following stroke, a recovery process is promptly initiated, which leads to a partial
      rehabilitation. However, a number of disabling residual symptoms may persist for years and
      include mental fatigue, depression, cognitive deficits, neurological problems and more. In
      the lack of an effective treatment these symptoms will lead to major consequences for the
      individual and the surrounding society. OSU6162 has in earlier clinical studies of stroke
      patients shown evidence of a favorable effect on residual symptoms, especially mental
      fatigue, together with a mild side effect profile.

      In this phase II, randomized, placebo-controlled, two-armed study, a 16 week OSU6162
      treatment will be compared to an equally long placebo treatment in patients with residual
      symptoms following stroke.
    

Detailed description: 
      Main objectives of this study are to evaluate the efficacy and safety of OSU6162 compared to
      placebo with respect to treatment response in post stroke patients.

      Endpoints:

      Primary endpoint is Clinical Global Impression of Change (CGI-C) after 16 weeks of treatment.

      Secondary endpoints are:

      CGI-C score after 4, 8 and 12 weeks of treatment. FAI; MFS; FSS; BDI; SF-36 scores after 4,
      8, 12 and 16 weeks of treatment. Correlation between plasma concentration of OSU6162 and
      therapeutic response after 4 and 16 weeks of treatment.

      Safety variables: AE/SAE, physical and neurological examinations, vital signs (blood pressure
      and puls) and laboratory test.

      Study Design:

      The treatment period is 16 weeks, during which all patients will make 7 study visits and have
      4 telephone interviews.

      Study visits include:

      Visit 1: screening at week -2, Days -14 to -5 Visit 2: baseline at week 0 Visit 4: week 4 ± 3
      days Visit 6: week 8 ± 3 days Visit 8: week 12 ± 3 days Visit 10: week 16 ± 3 days Visit 11:
      follow up at week 20 ± 7 days

      Randomization and start of treatment with OSU6162 or placebo at baseline, visit 2, week 0.
      Study medication administered during all study visits from baseline at visit 2 to visit 8 at
      week 12.

      Physical and neurological examinations, vital signs and weight recording during all study
      visits.

      ECG recorded during visits 1 (week -2) and 10 (week 16). Blood (and urine) sampling for
      safety labs during visits 1 (week -2), visit 4 (week 4), visit 10 (week 16). Pregnancy test
      at visit 1 and 10.

      Blood sampling for analysis of plasma OSU6162 concentration at visit 4 and 10.

      Primary outcome measures and secondary outcome self-assessment tests performed during all
      study visits.

      Telephone interviews at visit: 3 (week 2 ± 3 days), 5 (week 6 ± 3 days), 7 (week 10 ± 3 days)
      and 9 (week 14 ± 3 days.

      Concomitant medication, adverse events and drug compliance are recorded during all visits and
      telephone interviews.

      Dosing:

      All patients in the OSU6162 group start with a dose of 15 mg BID. The dose is increased to a
      maximum of 30 mg BID after 4 weeks of treatment. Intermediate doses are allowed and the final
      dose is individually flexible, depending on the therapeutic response and presence of AE. In
      the placebo group patients receive tablets with identical appearance to active treatment
      tablets (OSU6162 15 mg), administered according to the same dosing regime as active
      treatment.

      Data analysis and statistics:

      Efficacy analyses will be based on Mixed Models for Repeated Measures (MMRM) analyses. The
      MMRM analyses use all the longitudinal observations at each post-baseline visit for the study
      period of interest. Significance tests will be based on estimated population marginal means
      and Type III test of fixed effects, using a two-sided test with the significance level of
      0.05. Differences in distributions of categorical variables will be tested using the
      Chi-square test or Fisher's exact test.

      Due to the large number of variables engendered, multivariate statistical evaluations will be
      performed as a complement to the above-mentioned statistical methods.

      Before unblinding of the study data, a separate Statistical Analysis Plan (SAP) will be
      prepared.

      Patient and data safety:

      This study is conducted in accordance with the study protocol, the Declaration of Helsinki,
      ICH E6 GCP, the European Clinical Trials Directive 2001/20/EC and applicable local laws and
      regulations.

      The Investigator is responsible for ensuring the accuracy, completeness, legibility and
      timeliness of the data recorded in the CRFs. Data recorded in the CRF that are derived from
      source documents should be consistent with the source documents or the discrepancies should
      be explained. Signed sections of CRFs are monitored and collected on a regular basis.

      An individual secrecy agreement is established for all Sponsor, site personnel, independent
      auditors, and representatives from Competent Authorities that will have access to the
      information in the medical records for the participating patients.
    

Intervention name(s): OSU 6162; Placebo oral tablet
Intervention type(s): Drug; Drug
Intervention description(s): The active ingredient of OSU6162 is the S-enantiomer with the chemical name (S)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride. The substance is a white powder with a melting point of 177-182°C. Solubility in water is > 2000 mg/ml. Current laboratory code used is OSU6162-HCl. In trial protocol, OSU6162-HCl is shortened to OSU6162.; Circular coated tablet (with identical appearance to active treatment tablets 15 mg).
Other intervention name(s): OSU6162-HCl; PNU-9639 1A
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study is a randomised, placebo-controlled, parallel-group (two-armed) study of 16 weeks' treatment duration, comparing OSU6162 with placebo treatment in patients with residual symptoms after stroke.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: residual symptoms; mental fatigue; dopamine stabilizer