Evaluation of a New Thermostable Formulation of FLOLAN in Japanese Subjects

Cardiovascular Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02705807
• Other study ID #: 201614
• Status: Completed
• Phase: Phase 4
• First received: February 25, 2016
• Last updated: January 16, 2017
• Start date: May 2016
• Est. completion date: July 2016

Study information

• Verified date: January 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• FLOLAN injection with currently marketed diluent
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 with reformulated diluent
FLOLAN injection (epoprostenol 0.5 or 1.5) prepared with the reformulated diluent (epoprostenol sodium + pH 11.7 - 12.3 diluent) for Injection.

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Okayama

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with any adverse events (AE) and any serious AE (SAE)	An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect.	Up to 4 weeks
Primary	Percentage of subjects with any AE and any SAE	An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect.	Up to 4 weeks
Primary	Number of subjects with abnormal hematology parameters as a measure of safety	The following hematology parameters will be measured: Haemoglobin, hematocrit, red blood cell (RBC) count, white blood cell (WBC) count (including fractions), platelet count	Up to 4 weeks
Primary	Number of subjects with abnormal clinical chemistry parameters as a measure of safety	The following clinical chemistry parameters will be measured: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (Al-P), Gamma-Glutamyltranspeptidase (Gamma -GTP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total bilirubin, direct bilirubin, creatinine, sodium, magnesium, potassium, chloride, inorganic phosphorus, calcium, blood urea nitrogen (BUN), uric acid, glucose, total protein, albumin, thyroid function tests (triiodothyronine [T3], thyroxine [T4], thyroid-stimulating hormone [TSH])	Up to 4 weeks
Primary	Number of subjects with abnormal urinalysis parameters as a measure of safety	The following urinalysis parameters will be measured: Protein, sugar, and occult blood	Up to 4 weeks
Primary	12-lead Electrocardiogram (ECG)	A 12-lead ECG will be done in a supine position after having kept a subject at rest in this position for about 5 minutes at each assessment time.	Up to 4 weeks
Primary	Systolic and diastolic blood pressure as a measure of safety		Up to 4 weeks
Primary	Pulse rate as a measure of safety		Up to 4 weeks
Primary	Oxygen saturation	Oxygen saturation will be measured by pulse oximetry.	Up to 4 weeks
Secondary	The number of events to adjust dose of FLOLAN injection based on the change from baseline to 3 hours in mean Pulmonary Artery Pressure (mPAP) in a subset of subjects	The pulmonary artery pressure is a measure of the blood pressure found in the pulmonary artery.	Up to 4 weeks
Secondary	Number of subjects with the reason for the change dose of the new thermostable formulation of FLOLAN injection		Up to 4 weeks
Secondary	Change from baseline to Week4 in N-terminal Pro B-type Natriuretic Peptide (NT pro BNP)		Baseline and Week 4
Secondary	Change in World Health Organization (WHO) Functional Class frequency by visits and change from previous visit		Screening, Baseline and Week 4
Secondary	Change from baseline for mPAP in subjects who consent to undergo RHC	The pulmonary artery pressure is a measure of the blood pressure found in the pulmonary artery.	Baseline, at 24 hours after the first dose of thermostable formulation of FLOLAN injection, and Week 4
Secondary	Change from baseline for Pulmonary Vascular resistance (PVR) in subjects who consent to undergo RHC	PVR is the resistance to flow that must be overcome to push blood through the pulmonary vascular.	Baseline, at 24 hours after the first dose of thermostable formulation of FLOLAN injection, and Week 4
Secondary	Change from baseline for Cardiac Output (CO) in subjects who consent to undergo RHC	Cardiac output is the volume of blood pumped by the heart per minute.	Baseline, at 24 hours after the first dose of thermostable formulation of FLOLAN injection, and Week 4
Secondary	Change from baseline for Right Atrial Pressure (RAP) in subjects who consent to undergo RHC	RAP is the pressure of blood in the right atrium of the heart.	Baseline, at 24 hours after the first dose of thermostable formulation of FLOLAN injection, and Week 4