A double-blinded, randomized, crossover clinical study to assess the efficacy of Qutenza (capsaicin 8% patches) for the reduction of site pain caused by continuous subcutaneous infusion of Remodulin (treprostinil sodium), in Pulmonary Arterial Hypertension Patients - Efficacy of capsaicin 8% patches in Pulmonary Arterial Hypertension

• Register: EUCTR
• Last refreshed on: 28 August 2012
• Main ID: EUCTR2011-001312-59-GB
• Date of registration: 15/04/2011
• Prospective Registration: Yes
• Primary sponsor: Imperial College London
• Public title: A double-blinded, randomized, crossover clinical study to assess the efficacy of Qutenza (capsaicin 8% patches) for the reduction of site pain caused by continuous subcutaneous infusion of Remodulin (treprostinil sodium), in Pulmonary Arterial Hypertension Patients - Efficacy of capsaicin 8% patches in Pulmonary Arterial Hypertension
• Scientific title: A double-blinded, randomized, crossover clinical study to assess the efficacy of Qutenza (capsaicin 8% patches) for the reduction of site pain caused by continuous subcutaneous infusion of Remodulin (treprostinil sodium), in Pulmonary Arterial Hypertension Patients - Efficacy of capsaicin 8% patches in Pulmonary Arterial Hypertension
• Date of first enrolment: 24/06/2011
• Target sample size: 0
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001312-59
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: Certain members of the study centre will be unblinded. It is these members who will apply treatment. If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male or female patients 18 years or older with symptomatic PAH. 2.Willing to provide written informed consent to participate in the study. 3.With documented diagnosis of PAH, either idiopathic, familial or associated with connective tissue disease, congenital heart disease or the use of anorexogenic drugs. 4.Documented haemodynamic diagnosis of PAH by right heart catheterization – performed at any time prior to screening, showing: mean pulmonary arterial pressure >25 mm Hg, pulmonary capillary wedge pressure =/< 15 mmHg and pulmonary vascular resistance >240 dynes/sec/cm5. 5.Receiving stable doses of Remodulin® SC, continuously infused at a dose of at least 2.5 ng/kg/min for at least 8 weeks prior to enrolment. Additional medications that are approved for treatment of PAH (either bosentan or sildenafil) and other supplementary treatments such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. 6.History of pain at the site of Remodulin® SC infusion for at least 8 weeks prior to enrolment and as assessed on the 11 point pain intensity numerical pain rating scale (NPRS) from 0 to 10, where 0 represents “No pain" and 10 represents “Maximum pain imaginable”. Patients with a history of pain intensity equal or greater than 3 NPRS points (as determined by the NPRS trial diary completed during the screening period) are eligible to participate. [The use of systemic analgesics to relieve pain at the site of Remodulin® SC infusion, including salicylates, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, as well as topical analgesic-containing gels or creams (such as capsaicin 0.025% and 0.075% cream) and local anesthetics such as lidocaine are also permitted providing they remain unchanged for the entire duration of the study (i.e. from screening to the end of study follow up visit).] 7.Modified New York Heart Association (NYHA) (WHO) classification II-IV that has been stable for at least 8 weeks prior to enrolment. 8.A female subject is eligible to participate if she is of: •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <40 pg/ml (<140 pmol/L) is confirmatory]. •Child-bearing potential and agrees to use one of the following contraception methods: oAbstinence oContraceptive Methods with a Failure Rate of < 1%: - Oral contraceptive, either combined or progestogen alone; - Injectable progestogen; - Implants of levonorgestrel; - Estrogenic vaginal ring; - Percutaneous contraceptive patches; - - Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure rate as stated in the product label; - Male partner(s) sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study; - Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus vaginal spermicidal agent (foam/gel/film/cream/suppository).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Patient’s participating in another clinical trial or who have done so within 30 days before screening. 2.Patients with PAH in NYHA/WHO functional class I at screening. 3.Known to be positive for human immunodeficiency virus (HIV). 4.Patients with any additional medical condition or illness that, in the opinion of the Investigator would interfere with study compliance and/or impair the patient's ability to participate or complete the study. Concurrent diseases or conditions that may interfere with study participation or safety include bleeding disorders, arrhythmias, organ transplant, organ failure, current neoplasm, poorly controlled diabetes mellitus, poorly controlled hypertension, clinically significant haematological or biochemical abnormality, and serious neurological disorders. 5.Patients with a history of substance abuse (e.g. alcohol or drug abuse) within the previous 6 months before enrolment. 6.Patients with a history of severe allergies or multiple drug allergies and/or reported hypersensitivity to capsaicin. 7.Patients with no history of pain at the site of Remodulin® SC infusion or average pain intensity at screening less than 3 points on the numerical pain rating scale (NPRS). 8.Life expectancy less than 12 months. 9.Unable to provide informed consent. 10.Female patients who are lactating or pregnant (positive pre-randomisation serum pregnancy test) or plan to become pregnant during the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary arterial hypertension (PAH) is a rare life-threatening disease characterised by high blood pressure in the arteries to the lungs, rapidly evolving in a clinical syndrome of dyspnoea and fatigue and eventually leading to right ventricular failure and death.
MedDRA version: 13.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Trade Name: Qutenza
Product Name: Qutenza
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Capsaicin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 179-
Pharmaceutical form of the placebo: Transdermal patch
Route of administration of the placebo: Cutaneous use
Pharmaceutical form of the placebo: Cream
Route of administration of the placebo: Cutaneous use

Primary Outcome(s)

Primary end point(s): The primary outcome measure of safety will be based on the incidence, intensity and type of AEs and clinically significant changes in vital signs (pulse rate, blood pressure, respiration rate, pulse oximetry and temperature), and changes in concomitant medications throughout the study. Evaluation of safety will also be based on subject’s physical examination, signs and symptoms of PAH, routine clinical laboratory tests (hematology, chemistry, coagulation panel, and urinalysis), ECG, and NYHA (WHO) classification at the screening and end of study follow up visits.

Main Objective: The primary objectives of this study are to determine: 1.The safety and tolerability of a single application of Qutenza® (capsaicin 8% patch) in pulmonary arterial hypertension patients. 2. The efficacy of a single application of Qutenza® (capsaicin 8% patch) in improving site pain caused by continuous SC infusion of Remodulin® in pulmonary arterial hypertension patients, relative to transparent adhesive control dressing (Tegaderm film 10cmx12cm) in combination with 0.075% capsaicin cream (Axsain®), as assessed by the change in Numerical Pain Rating Scale (NPRS) from baseline.

Secondary Objective: The secondary objective of this study is to determine: The efficacy of a single application of Qutenza® (capsaicin 8% patch) in reducing site pain caused by continuous SC infusion of Remodulin®, in pulmonary arterial hypertension patients, relative to transparent adhesive control dressing (Tegaderm film 10cmx12cm) in combination with 0.075% capsaicin cream (Axsain®), as assessed by: Patient Global Impression of Change (PGIC) relative to Remodulin® SC repositioning on the day of screening. The change in area of cutaneous hypersensitivity around the infusion site (optional and when feasible) [assessed using 1) cotton wool, 2) brush, 3) monofilaments, 4) pin prick and 5) thermal thresholds], relative to Remodulin® SC repositioning on the day of screening. The reduction in area of skin axon reflex vasodilatation (skin flare) around the infusion site (optional and when feasible) [assessed using 1) visual tracing of area of redness, and 2) laser Doppler fluxmetry], relative to Remod

Secondary ID(s)

CRO1824