Bioequivalence - Duodart Against Avodart & Omnic
Condition: Prostatic Hyperplasia
MeSH terms: Prostatic Hyperplasia; Hyperplasia
Study type: Interventional
Phase: Phase 1

Summary: 
      Open-label, randomized, single dose, two-treatment, two-way crossover study
    

Detailed description: 
      The present study is planned to establish bioequivalence of Duodart® 0.5mg/0.4mg manufactured
      by GlaxoSmithKline to concomitant dosing with separate capsules of dutasteride 0.5 mg and
      tamsulosin hydrochloride 0.4 mg formulations commercially available in Russia. The design of
      the present study relies on data obtained in pivotal bioequivalence study and Russian
      guidance on high quality bioequivalence studies.

      Summary of treatment groups Treatment Sequence Number of subjects

        1. 18

        2. 18 Total number of subjects 36 Eligible subjects will be admitted to the research unit
           one day prior to dosing (Day 0) and will remain as inpatients until approximately 72
           hours after dosing. Subjects will undergo a washout period of approximately 28 days from
           each dose of study medication. During washout period subjects will be contacted via
           telephone within approximately 10-14 days after the dosing for the collection of
           information about adverse events and medications taken by volunteers during washout
           period Overall study duration could be about 2 months - Screening up to 21 days + 10
           days (5 days of each of 2 treatment periods) + 28 days washout period between treatment
           administration + 10-14 days of follow up period.

      Upon completion of the last dosing session, subjects will be contacted via telephone within
      approximately 10-14 days for a follow-up inquiry (or visit at the discretion of the
      investigator) and will be subsequently discharged from the study.

        -  Order of Assessments and Procedures

      Where multiple measurements/evaluations are scheduled for the same time then the
      measurements/evaluations will be taken in the following order:

        1. Vital Signs

        2. Orthostatic Vital Signs

        3. PK - Blood Sample Where multiple measurements/evaluations are scheduled for the same
           time then the study co-coordinator will attempt to ensure that the PK samples are drawn
           as close to the scheduled time as possible whilst adhering to the order of assessments
           as described above.

             -  Blinding and Randomisation On Day 0 of the first treatment period, subjects will be
                randomly allocated at the ratio of 1:1 to one of 2 treatments (refer to Table 1),
                according to a computer-generated randomisation list. CRO will generate the
                randomisation list. For the purpose of randomisation screening numbers of
                volunteers will be used; randomisation numbers will not be assigned to study
                subjects.

      Treatment will be open-label; therefore, blinding procedures are not applicable.

        -  Number of Subjects Approximately 50 healthy male subjects will be screened to allow 36
           eligible subjects to be randomized and ensure that 30 subjects complete the study
           according to the protocol without violations.

        -  PHARMACOKINETIC PARAMETERS

        -  Drug assay Dutasteride and tamsulosin will be extracted from human plasma by
           liquid-liquid extraction using organic solvent. Extracts will be analysed by validated
           high-performance liquid chromatography - mass spectrometry. The lower limit of detection
           is about 0.1ng/mL

        -  Calculation of Pharmacokinetic Parameters Pharmacokinetic parameters will be computed
           for each subject and treatment using standard methods as described in Appendix II.

      For tamsulosin, the following PK parameters will be computed:

        -  Cmax

        -  Tmax

        -  AUC(0-t)

        -  AUC(0-∞)

        -  Half-life

        -  Mean residence time

      For dutasteride, the following PK parameters will be computed:

        -  Cmax

        -  Tmax

        -  AUC(0-t)

        -  Mean residence time The half-life and AUC(0-∞) will be computed only for tamsulosin
           because duration of sampling period equal to 72 h is expected to be non-sufficient for
           reliable computation of half-life and AUC(0-∞) of dutasteride given the complex
           pharmacokinetics of dutasteride and long half-life of dutasteride at each of two
           elimination pathways [12].

             -  ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) The investigator or site staff
                is responsible for detecting, documenting and reporting events that meet the
                definition of an AE or SAE.

      AEs will be collected from the start of Study Treatment and until the follow-up contact.

      SAEs will be collected over the same time period as stated above for AEs. However, any SAEs
      assessed as related to study participation (e.g. study treatment, protocol-mandated
      procedures, invasive tests, or change in existing therapy) or related to a GSK product will
      be recorded from the time a subject consents to participate in the study up to and including
      any follow-up contact. All SAEs will be recorded and reported to GSK within 24 hours

        -  LIFESTYLE AND/OR DIETARY RESTRICTIONS

        -  Meals and meal composition Subjects will be required to fast for approximately 10 hours
           prior to dosing, with the exception of water, which will be allowed freely except for 1
           hour before and 1 hour after dosing.

      Following dosing, subjects will not be allowed food until 4 hours post dose. Meals will be
      served at the times outlined in Section 2 (Schedule of Assessments), in a seated position
      (unless orthostasis detected, in which meals should be served in a semi-recumbent position).

      Meals will be served on Days 2 and 3 at approximately the same time as on Day 1.

      Subjects will not be allowed to consume the following foods or drinks within 7 days prior to
      the first dose of study medication until after collection of the final pharmacokinetic blood
      sample: grapefruit juice; red wine; grapefruit or cruciferous vegetables (watercress,
      broccoli, cabbage, Brussels sprouts).

        -  Dosage and Administration One Duodart® 0.5mg/0.4mg capsule as Test formulation or one
           Avodart® 0.5 mg and one Omnic® 0.4 mg capsules as Reference formulation will be
           administered in the morning of Day 1 in each study period. The capsules should not be
           opened or chewed, but swallowed whole with 200 mL of water at room temperature

        -  STATISTICAL METHODS

        -  Population for analysis For pharmacokinetics parameters calculation and statistical
           analysis, the data received from no less than 30 volunteers who have completed the study
           according to the Protocol will be explored.

      Safety analysis population of this study will consist of all volunteers who took part in at
      least one study stage.

      Data from volunteers who discontinued the study prematurely will be included in the final
      report, but no included in the pharmacokinetics parameters calculation and statistical
      analysis.

      If the volunteer has not taken any of the study drugs at all, his/her data are not to be
      included in the statistical analysis.

        -  Analysis Method For pharmacokinetics parameters calculation, statistical analysis, and
           results presentation statistical packages (Statistics, Microsoft Excel 2007, SAS, or
           SPSS) will be used.

      Descriptive statistics will be used to present the mean value, standard deviation, median
      value, minimal and maximal value.

      Analysis of variance will be done based on the assumption about the log-normal distribution
      of AUC, Cmax, and Cmax/AUC, and normal distribution of other pharmacokinetics parameters
      except tmax. The comparison of average values of the investigated and comparator drug
      parameters is performed with the multiplicative model as a basis and confidence intervals
      built for the ratio of the corresponding mean values. After the logarithmic transformation
      these values will be analyzed by analysis of variance (ANOVA).
    

Intervention name(s): dutasteride/tamsulosin; dutasteride; tamsulosin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Duodart® 0.5 mg / 0.4 mg - 1 dose at Day 1 of each treatment period. There are 2 treatment periods separated by approximately a 28-day washout period. All study drugs will be administered orally as capsules; Avodart® 0.5 mg together with Omnic® 0.4 mg - 1 dose at Day 1 of each treatment period. There are 2 treatment periods separated by approximately a 28-day washout period. All study drugs will be administered orally as capsules; Omnic® 0.4 mg together with Avodart® 0.5 mg - 1 dose at Day 1 of each treatment period. There are 2 treatment periods separated by approximately a 28-day washout period. All study drugs will be administered orally as capsules
Other intervention name(s): Duodart® 0.5 mg / 0.4 mg; Avodart® 0.5 mg; Omnic® 0.4 mg
Intervention MeSH terms: Tamsulosin; Dutasteride
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment