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Evaluating the effect of Loratadine associated with Rapamune in Lymphagioleiomyomatosis (LAM).

Phase 1
Conditions
EFFECT OF LORATADINE ON LYMPHANGIOLEIOMYOMATOSIS
MedDRA version: 21.0Level: PTClassification code 10049459Term: LymphangioleiomyomatosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Registration Number
EUCTR2020-000702-29-ES
Lead Sponsor
IDIBELL (Institut d’Investigació Biomédica de Bellvitge)
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Female
Target Recruitment
62
Inclusion Criteria

Patients with LAM and > 18 years-old with:
- FEV1 > 35% and DLCO > 20%
- Oxygen saturation (SpO2) > 85% by pulse oximetry while breathing ambient air at rest.
- Patients with a definite diagnosis consistent with LAM prior to screening based on International consensus criteria within 10 years prior to randomization.
- HRCT within 12 months prior to randomization with central reading demonstrating a radiological pattern suggesting LAM and some other criteria for initiating sirolimus (symptoms, FEV1 decline or the presence of abdominal lynphangioleiomiomas).
- Taking stable doses of rapamycin for at least the last 3 months.
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 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

- Concomitant use of other HR1 antagonist.
- Hypersensitivity to HR1 antagonists.
- Current smoker or ex-smoker having quit smoking < 4 months prior to firs screening visit.
- Use of systemic immunosuppressants or chemotherapy within 30 days of screening.
- Receiving oral corticosteroids>15mg/day, vasodilator therapies for pulmonary hypertension (e.g., bosentan), unapproved and/or investigational therapies for LAM or administration of such therapies within 4 weeks of initial screening.
- At baseline/screening visit, values of liver transaminases above 3 times upper limit, alkaline phosphatase above 2.5 times upper limit, or bilirubin above 1.5 times upper limit.
- Creatinine clearance (CrCl)<60ml/min (determined by Cockcroft-Gault Equation) at baseline/screening visit.
- Patients treated with strong inhibitors and inducers of CYP either during the study or 14 days prior to enrolment in the study: antifungals (e.g., ketoconazole, itraconazole), clarithromycin, telithromycin, cobicistat, protease inhibitors (e.g., atazanavir, ritonavir, and saquinavir) and grapefruit juice, phenytoin, carbamazepine, barbiturates, rifampin.
- Current allergic asthma or other major allergic diseases that requires different daily antihistaminic treatment.
- History of coexistent and clinically significant (in the opinion of the Investigator) chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, inadequately treated sleepdisordered
breathing, or any clinically significant pulmonary diseases other than LAM.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Evaluate the safety profile of loratadine in combination with rapamycin after 52 weeks <br>Assess security (incidence of adverse events according to their<br>intensity, severity, relation to treatment) of the combination of loratadine and rapamycin compared with rapamycin in monotherapy in patients with LAM.;Secondary Objective: The secondary objectives evaluate: <br>a) quality of life and progression free-survival time, <br>b) changes in the established LAM serum biomarker VEGFD,<br>c) the utility of the major histamine-derived metabolite methylimidazoleacetic acid (MIAA) for monitoring disease progression and biological treatment effect.;Primary end point(s): Incidence of adverse effects associated with taking loratadine associated with rapamycin, including nausea, diarrhea, abdominal pain, vomiting, headache, hypertransaminasemia.;Timepoint(s) of evaluation of this end point: The assessment of the primary point is at 52 weeks
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): -Progression-free survival time, which will be considered when some of these events are present: FEV1 decrease > 10%, DLCO decrease > 15%, lung transplant, death.<br>-Hospitalization. Registration of any cause of hospitalization;Timepoint(s) of evaluation of this end point: The assessment of the primary point is at 52 weeks
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