Evaluation of a New Thermostable Formulation of FLOLAN in Japanese Subjects

An Open Label, Single-arm Study Evaluating a New Thermostable Formulation of FLOLAN™ in Japanese Subjects With Pulmonary Arterial Hypertension (PAH)

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.

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.