E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049459 |
E.1.2 | Term | Lymphangioleiomyomatosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049459 |
E.1.2 | Term | Lymphangioleiomyomatosis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Does doxycycline prevent matrix metalloproteinase dependent tissue destruction in lymphangioleiomyomatosis (LAM) thus preserving lung function, exercise capacity and quality of life in LAM? |
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E.2.2 | Secondary objectives of the trial |
(1) determine the optimum dose of doxycycline needed to suppress MMP production (2) define the safety profile of doxycycline in LAM (3) provide evidence of efficacy and size of effect (4) determine the optimum design and logistics of future trials.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Sporadic LAM diagnosed either by cystic lung disease on HRCT classical of LAM plus angiomyolipoma or chylous effusion or cystic lung disease on HRCT and tissue biopsy showing LAM or angiomyolipoma • TSC-LAM diagnosed by cystic lung disease on HRCT and tuberous sclerosis diagnosed by modified Gomez criteria. • Patients with either an FEV1 below 80% predicted or evidence of a 20% deterioration in FEV1. • Hormone and bronchodilator treatment for LAM* is allowed providing treatment has not changed in the three months prior to enrolment. * progesterone, GnRh agonists and bronchodilators.
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E.4 | Principal exclusion criteria |
• Inability to give informed consent. • Mental retardation. • Age less than 18 years. • Pneumothorax, chylous effusion, bleeding angiomyolipoma or change in hormone treatment within 3 months. • Previous organ transplantation. • Severe or uncontrolled epilepsy. • Use of any oral contraceptive pill. • Pregnancy or breast feeding. Pre-menopausal patients must be willing to use appropriate birth control measures to avoid pregnancy while enrolled in the study. • Major systemic diseases (malignancy, myocardial infarction or unstable angina, type1 diabetes, severe hypertension, liver cirrhosis). • Use of drugs known to interact with doxycycline, including anticoagulation with warfarin. • Anticoagulation with warfarin. • Hypersensitivity to tetracyclines. • Treatment with mTOR inhibitor within the previous 3 months (sirolimus, everolimus). • Use of doxycycline or other experimental drug within the previous three months.
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean rate of change of FEV1/year over 24 months on doxycycline compared with placebo. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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To avoid withholding treatment to those who decline rapidly in the placebo group, patients with either a fall from baseline FEV1 of 300 ml or a fall in resting SaO2 of 3% (on two occasions at least 2 weeks apart) will be offered doxycycline according to the protocol. Those deteriorating in the doxycycline group will be withdrawn from the study. Patients with either recurrent pneumothorax, increase in chylous effusion or bleeding angiomyolipoma will be withdrawn. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |