Study of a New Thermo Stable Formulation of Epoprostenol Sodium to Treat Pulmonary Arterial Hypertension (PAH)

Browse trials for

• Pulmonary Arterial Hypertension 761
• Hypertension, Pulmonary 1,105
• Hypertension 6,687

Keywords

• flolan
• pulmonary arterial hypertension
• thermo stable formulation
• epoprostenol sodium
• modified sterile diluent

Pulmonary Arterial Hypertension

761 studies on the registry are indexed under Pulmonary Arterial Hypertension; 142 are open to participants now.

This study's enrollment of 16 is below the median of 38 across 509 interventional studies indexed under Pulmonary Arterial Hypertension.

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Study arms

• Experimental
  All subjects

  Subjects enter the study already taking current marketed FLOLAN (epoprostenol sodium) and continue for 4 weeks (run-in). At baseline, they will be swopped to the new thermo stable formulation of epoprostenol sodium for 4 weeks (or longer if they continue in the extension phase of the study).

  Drug: current marketed FLOLAN (epoprostenol sodium) · Drug: new thermo stable formulation of epoprostenol sodium

Interventions

• Drugcurrent marketed FLOLAN (epoprostenol sodium)

  continuous intravenous infusion

• Drugnew thermo stable formulation of epoprostenol sodium

  continuous intravenous infusion

Primary outcomes

1. Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)

   Subject-rated measure of health status comprised of 36 items: 8 subscale scores (physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health), 2 summary scores (physical component and mental component), and a self-evaluated change in health status. Subscale and summary scores range: 0-100. Higher subscale and summary scores was considered as better health status. Change from Baseline was calculated as score at observation minus score at baseline. Baseline was defined as Visit 2 i.e. Day-14 (+ or - 7 days).

   Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3)

2. Change From Baseline in Study Specific Participant Acceptance Survey

   Study-specific questionnaire comprised the pre-defined15 questions which included activities of daily living assessment. Participants rated the question on a scale of 1 to 10, where 1 was do not agree and 10 was strongly agree. Change from Baseline was calculated as score at observation minus score at Baseline. Changes from Baseline was assessed for Questions 2 to 12. Baseline was defined as Visit 2 i.e. Day-14 (+ or - 7 days).

   Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3).

3. Change From Baseline in Dose of Thermo Stable Epoprostenol Sodium at Week 4

   Dose titration requirement was assessed at the time of discharge. Change from Baseline was calculated as score at observation minus score at Baseline. Units- nanogram per kilogram per minute (ng/kg/min). Baseline was Visit 2 i.e . Day-14 (+ or - 7 days).

   Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4

Secondary outcomes

1. Number of Participants With Any Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events(SAEs)

   An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, congenital anomaly/birth defect and medically significant and all events of possible drug-induced liver injury with hyperbilirubinaemia. Only treatment emergent AEs and SAEs were reported in this outcome measure. Specifically, this study reported 2 SAEs, but only 1 was categorized as treatment emergent.

   Time frame: Up to visit 3 (Week 4)

2. Number of Participants With Infusion Site Reactions During Treatment Period

   Infusion site reactions were reported during the treatment period. Infusion site was inspected for erythema, excoriation, induration, skin necrosis or signs of local sepsis.

   Time frame: Baseline visit (Visit 2) to Week 4 (Visit 3)

3. Change From Baseline in Vital Signs at Week 4 : Systolic and Diastolic Blood Pressure

   Systolic blood pressure is a measure of blood pressure while the heart is beating. Diastolic blood pressure is a measure of blood pressure while the heart is relaxed. Change from Baseline was calculated as the value at the indicated time points minus the value at Baseline. Baseline was Visit 2 i.e. Day-14 (+ or - 7 days).

   Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4(Visit 3)

4. Change From Baseline in Vital Signs at Week 4: Heart Rate

   Summary mean change in heart rate measured in beats per minute (beats/min or BPM). Change from Baseline was calculated as the value at the indicated time points minus the value at Baseline. Baseline was Visit 2 i.e. Day-14 (+ or - 7 days).

   Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4

5. Number of Participants With Abnormal Clinical Chemistry

   Abnormal clinical chemistry was analyzed as follows: serum alanine aminotransferase (ALT/SGPT) \>= 3 x upper limit of normal (ULN) , aspartate aminotransferase (AST/SGOT) \>= 3 x ULN , total bilirubin \>= 34.2, creatinine \>= 176.8.

   Time frame: Up to 1 week after Week 4 (Follow-up)

6. Number of Participants With Abnormal Hematology

   Values for hemoglobin, hematocrit, and platelet count were analyzed. Participants with abnormal values have been reported. The low and high value concern were as follows: hemoglobin (Males \< 98, \>180.0) (females \<91, \>161.0)grams per litre (g/L); hematocrit (Males \< 32.0, \>54.0) (females \<29.0, \>50.6) fraction (1); platelet count (\< 100, \> 500) gram international units per litre (gI/L).

   Time frame: Up to 1 week after Week 4 (Follow-up)

7. Number of Participants With Abnormal Urinalysis

   Dipstick method was used to measure blood, glucose and protein. Data was analyzed up to 1 week after Week 4 (Follow-up visit).

   Time frame: Up to 1 week after Week 4 (Follow-up)

8. Change From Baseline in Six Minute Walk Distance Test (6MWD) After 4-weeks of Treatment

   This assessment was a non-encouraged test that measures the distance walked for a duration of 6 minutes. Change from Baseline was calculated as value at observation minus value at Baseline. Baseline visit was Visit 2 i.e. Day-14 (+ or - 7 days).

   Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4

9. Breathlessness After 6MWD - Borg Dyspnoea Index (BDI)

   The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test. The BDI scale was assessed by each participant. Change from Baseline = score at observation minus score at Baseline. Baseline visit was Visit 2 i.e. Day-14 (+ or - 7 days).

   Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4

10. World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment

    World Health Organization functional class was analyzed as class I, class II, class III and class IV. World Health Organization functional class was analyzed at Baseline (Visit 2 i.e. Day-14 \[+ or - 7 days\]) and Week 4. The classed were defined as Class I: No symptoms of pulmonary arterial hypertension with exercise or at rest, Class II: No symptoms at rest but uncomfortable and short of breath with normal activity, Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting and Class IV: Symptoms at rest and severe symptoms with any activity. Hence the severity increased from class I (better) to Class IV (worse).

    Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4

11. Mean Oxygen Saturation in Blood Over Time

    Pulse oximetry (oxygen saturation) was analyzed. Data for Pulse oximetry (oxygen saturation) was analyzed up to the treatment follow up (1 week after Visit 3 \[Week 4\]).

    Time frame: up to the treatment follow up (1 week after Visit 3 [Week 4])

12. Number of Participants With Urine Pregnancy Test Positive

    Urine samples were collected for urine pregnancy test. Urine samples were collected at up to the treatment follow up (1 week after Visit 3 \[Week 4\]). Number of participants with urine pregnancy test positive has been reported.

    Time frame: up to the treatment follow up (1 week after Visit 3 [Week 4])

Baseline characteristics

Publications

• Provencher S, Paruchuru P, Spezzi A, Waterhouse B, Gomberg-Maitland M; pH12 Flolan reformulation study group. Quality of life, safety and efficacy profile of thermostable flolan in pulmonary arterial hypertension. PLoS One. 2015 Mar 20;10(3):e0120657. doi: 10.1371/journal.pone.0120657. eCollection 2015. PubMed 25793960 ↗