Evaluation of a New Thermostable Formulation of FLOLAN in Japanese Subjects
Condition: Cardiovascular Disease
MeSH terms: Pulmonary Arterial Hypertension; Cardiovascular Diseases
Intervention: FLOLAN injection with currently marketed diluent; FLOLAN injection with reformulated diluent
Intervention description: FLOLAN injection (epoprostenol 0.5 or 1.5) prepared with the currently marketed diluent (epoprostenol sodium+ powder of hydrogen [pH] 10.2 - 10.8 diluent) for Injection.; FLOLAN injection (epoprostenol 0.5 or 1.5) prepared with the reformulated diluent (epoprostenol sodium + pH 11.7 - 12.3 diluent) for Injection.
Intervention MeSH terms: Epoprostenol; Tezosentan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Pulmonary Arterial Hypertension (PAH); safety; FLOLAN; New Thermostable Formulation; dose adjustment; reformulated diluents; currently marketed diluent

Summary:

      This study is a Phase IV, open-label, single-arm study to assess the safety and the necessity
      of dose adjustment after switching to FLOLAN injection prepared with the reformulated diluent
      in Japanese patients with PAH who are receiving higher doses of FLOLAN injection than in
      other countries. The objective is to evaluate the safety and tolerability of the thermostable
      formulation of FLOLAN injection (that is [i.e.], FLOLAN injection prepared with the
      reformulated diluent) when switched from the existing FLOLAN injection treatment (i.e.,
      FLOLAN injection prepared with the currently marketed diluent). The study will include a
      screening visit, a run-in period of a maximum of 4 weeks with the existing FLOLAN treatment
      (i.e., FLOLAN injection prepared with the currently marketed diluent), a 4-week treatment
      period with the thermostable formulation of FLOLAN injection (i.e., FLOLAN injection prepared
      with the reformulated diluent) and a one-week follow-up visit. Adequate number of subjects
      will be enrolled in the study in order to have 10 subjects to complete assessments at 4
      weeks, including at least 5 subjects as a subset of subjects who consent to undergo right
      heart catheterisation (RHC) over 24-hour and at Week 4. FLOLAN is a registered trademark of
      the GlaxoSmithKline [GSK] group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects at least 18 to 75 years at the time of screening;

          -  Subjects must be on FLOLAN therapy for pulmonary arterial hypertension (PAH) as
             approved in the product label;

          -  Subjects must receive FLOLAN therapy at 45 nanograms (ng)/kilogram (kg)/minute (min)
             or higher;

          -  Subjects must be on stable doses of their existing FLOLAN treatment for a minimum of
             one month prior to screening; it is acceptable to adjust within 10% of dose during the
             last one month period;

          -  Subjects must be on stable doses of any current PAH treatments other than FLOLAN
             therapy in the last 30 days prior to screening;

          -  Subjects who meet any of the following: A female subject is eligible to participate if
             she is not pregnant (as confirmed by a negative [serum or urine] human chorionic
             gonadotrophin [hCG] test), not lactating, and at least one of the following conditions
             applies:

               -  Non-reproductive potential defined as: Pre-menopausal females with any of the
                  following: documented tubal ligation, documented hysteroscopic tubal occlusion
                  procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy,
                  or documented bilateral oophorectomy. Postmenopausal defined as 12 months of
                  spontaneous amenorrhea (in questionable cases a blood sample with simultaneous
                  follicle stimulating hormone [FSH] and estradiol levels consistent with
                  menopause). Females on hormone replacement therapy (HRT) and whose menopausal
                  status is in doubt will be required to use one of the highly effective
                  contraception methods if they wish to continue their HRT during the study.
                  Otherwise, they must discontinue HRT to allow confirmation of post-menopausal
                  status prior to study enrolment.

               -  Reproductive potential and agrees to follow one of the options listed below in
                  the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in
                  Females of Reproductive Potential (FRP) from 30 days prior to the first dose of
                  thermostable formulation of FLOLAN therapy until completion of the follow-up
                  visit.

          -  Subject must agree not to participate in a clinical study involving another
             investigational drug or device throughout this study;

          -  Subjects must be competent to understand the information given in the Institutional
             Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent
             form and must sign the form prior to the initiation of any study procedures.

        Exclusion Criteria:

          -  Subjects who are given FLOLAN therapy for a condition or in a manner that is outside
             the approved indication.

          -  Subjects with congestive heart failure arising from severe left ventricular
             dysfunction.

          -  Subjects, with or without supplemental oxygen, who have a resting arterial oxygen
             saturation (SaO2) <90% as measured by pulse oximetry at screening.

          -  Subjects have been hospitalised as an emergency or visited the emergency room for a
             condition related to PAH or treatment for PAH in the last 3 months.

          -  The subject's clinical condition is such that they are not expected to remain
             clinically stable for the duration of the study.

          -  Female subjects who are pregnant or breastfeeding.

          -  Subjects who have demonstrated noncompliance with previous medical regimens.

          -  Subjects who have a history of abusing alcohol or illicit drugs within 1 year.

          -  Subjects who have participated in a clinical study involving another investigational
             drug or device within four weeks before screening.

          -  Any concurrent condition that would affect the safety of the subject or in the opinion
             of the investigator (or subinvestigator) it is not in the best interest of the patient
             to participate in the study.