Proof of Concept Study to Investigate the Efficacy, Haemodynamics and Tolerability of Terguride vs. Placebo in Patients with Pulmonary Arterial Hypertension. Double-blind, randomized, prospective Phase II proof of concept study for 12 weeks of constant treatment with Terguride or placebo. Having finished this proof-of-concept study it is intended that patients will continuously be treated in an open label extension on a voluntary basis.

Phase 2

Completed

Conditions: high pulmonary blood pressure
pulmonary arterial hypertension
10019280

Registration Number: NL-OMON35522

Lead Sponsor: ErgoNex Pharma GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Female and male patients of any racial origin with PAH (WHO classification II-IV)
2. On stable treatment with best supportive care with anticoagulant drugs, diuretics, cardiac glycosides, supplemental oxygen and calcium channels blockers, adjusted to the individual need of the respective patient. Specific PAH mono-therapy (or combination-therapy not exceeding two PAH specific drugs) with either endothelin receptor antagonists or phosphodiesterase type 5 inhibitors or non-parenteral prostanoids (i.e. inhaled, oral, s.c.) is allowed (pre-treated patients) but not mandatory (treatment naive patients). Patients already on PAH specific drugs must be receiving a stable dose of the medication for at least 3 months
3. Having fulfilled his/her 18th birthday on Day 1 of the study but not older than 80 years (up to the patient*s 81st birthday).
4. PAH due to idiopathic pulmonary arterial hypertension or connective tissue disease associated PAH
5. Right heart catheterisation 4 weeks prior to screening or at screening with PAH, specifically PAPm *25 mmHg (at rest), Pulmonary capillary wedge pressure (PCWP) *16 mmHg, pulmonary vascular resistance *500 dyn x sec x cm-5. Echocardiogram at screening consistent with PAH, specifically evidence of right ventricular hypertrophy or dilation, evidence of normal left ventricular function, and absence of mitral valve stenosis
6. Six minutes walk distance above 150 m
7. Receiving conventional PAH therapy, stable for one month.
8. Presentation of negative test results in regard to HIV, Hepatitis C/B, not older than 4 weeks.
9. Able to understand and willing to sign the Informed Consent Form.

Exclusion Criteria

1. PAH of any cause other than permitted in the entry criteria
2. Contraindication for heart catheterisation
3. Any change in disease-targeted therapy within the last month before screening
4. Patients requiring intravenous prostanoid therapy within 3 months prior to study start
5. Any subject who had received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study
6. Known intolerance to Terguride
7. Active liver disease, porphyria or elevations of serums transaminases >3 x ULN (upper limit of normal) or bilirubin > 1.5 x ULN
8. History or suspicion of inability to cooperate adequately.
9. Cancer or other malign haematological disease
10. Pulmonary Hypertension caused by left heart disease
11. Pulmonary Arterial Hypertension associated with congenital heart disease (PAH-CHD)
12. Pulmonary Arterial Hypertension associated with human immunodeficiency virus infection (PAH-HIV)
13. Portopulmonary Hypertension (PPHT)
14. CTEPH Chronic Thromboembolic Pulmonary Hypertension
15. Pulmonary Hypertension associated with other diseases excluding aforementioned: PAH due to idiopathic pulmonary arterial hypertension or tissue disease associated PAH, PAH associated with connective tissue disease including systemic sclerosis (sclerodermia) and systemic lupus erythematosus (SLE).
16. Pulmonary Hypertension associated with other chronic lung diseases
17. Additionally, women with child bearing potential must be excluded if:
* They have not used reliable contraception in the cycle before
the study. According to CPMP/ICH/286/95 (modification) highly
effective methods of birth control (defined by a failure rate
< 1% per year) include the consistent and correct use of
implants, injectables combined oral contraceptives, selected
intrauterine devices (IUD), sexual abstinence or vasectomised
partner. The subject has to agree to continue using such highly
reliable contraception during the entire study period and the
cycle after the study
* They are pregnant or lactating. (A negative pregnancy test must be provided for all patients)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint is the investigation into:<br /><br>Pulmonary vascular resistance at final right heart catheterisation (15 weeks<br /><br>from initial right heart catheterisation) as objective measure<br /><br>Benchmark: significant reduction (20% vs. baseline) of pulmonary vascular<br /><br>resistance<br /><br><br /><br>In the open-label extension procedure safety parameters and time to clinical<br /><br>worsening will be addressed. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are to evaluate the effects of the treatment regimen on:<br /><br>1. Time from randomisation to clinical worsening (defined as the combined end<br /><br>point of death, lung transplantation, hospitalisation for pulmonary<br /><br>hypertension, leading to discontinuation or need for additional specific PAH<br /><br>therapy)<br /><br>2. Change in six minutes walk distance (baseline/ 15. week)<br /><br>3. Change in Borg Dyspnea Index (baseline/ 15.week)<br /><br>4. Change in WHO functional class (a modification of the New York Heart<br /><br>Association class; baseline/15. week)<br /><br>5. Change in cardiac output-index<br /><br>6. Change in PA pressure<br /><br>7. Circulating levels of NT-pro-BNP (baseline/ 15. week)<br /><br>8. Quality of life questionnaire (SF 36, baseline/ 15. week)<br /><br>9. Adverse events<br /><br>10. Concomitant medication</p><br>