LOSARTAN POTASSIUM, HYDROCHLOROTHIAZIDE for Osteogenesis imperfecta

Inclusion criteria

• {"criterion_text":"- Age 16 years and above"}
• {"criterion_text":"- Prior treatment with more than 6 weeks of oral or more than one single intravenous bisphosphonate therapy is allowed provided there has been a 10-year washout period since the last dose of treatment."}
• {"criterion_text":"- Subjects not eligible (i.e., safety, tolerability and/or compliance issues, investigator’s judgement, etc.) or do not have access to the authorized products (i.e., neridronate in Italy)."}
• {"criterion_text":"- Prior treatment with more than a single dose of denosumab is allowed provided there has been a 1-year washout period since the last dose of treatment."}
• {"criterion_text":"- Diagnosed with osteogenesis imperfecta (any type)"}
• {"criterion_text":"- Prior treatment with up to and including 6 weeks of oral bisphosphonate therapy is allowed provided there has been a 12 month washout period since the last dose of treatment."}
• {"criterion_text":"- Prior treatment with a single dose of an intravenous bisphosphonate is allowed provided there has been an 18 month washout period since the treatment was given"}
• {"criterion_text":"- A women of childbearing potential (WOCBP) who agrees to use an effective method of contraception from point of signing the informed consent throughout the study."}
• {"criterion_text":"- Agreed not to participate in another interventional research project during their involvement in this study."}
• {"criterion_text":"- Not taking prohibited concomitant medications, listed in exclusion criteria"}
• {"criterion_text":"- Does not have any other contraindication that makes the patient unsuitable to take part in the study in the opinion of the investigator."}

Exclusion criteria

• {"criterion_text":"- Current use of losartan"}
• {"criterion_text":"- Known hypersensitivity to losartan or any of the excipients"}
• {"criterion_text":"- Prior use of losartan within preceding 6 month to enrolment"}
• {"criterion_text":"- Recent fracture in the prior 6 months to enrolment"}
• {"criterion_text":"- Presence of other chronic illnesses including renal failure likely to affect bone metabolism or structure. GFR in children will be assessed using the Bedside Schwartz equation"}
• {"criterion_text":"- Known severe hypotension resulting in dizziness, fainting or headaches"}
• {"criterion_text":"- Hyperkalaemia"}
• {"criterion_text":"- Current medication that increases potassium retention, or may increase potassium levels, such as potassium-retaining diuretics"}
• {"criterion_text":"- Current medication with lithium"}
• {"criterion_text":"- Current medication with other substances which may induce hypotension"}
• {"criterion_text":"- Currently taking oral bisphosphonates or intravenous bisphosphonates"}
• {"criterion_text":"- Prior treatment with more than 6 weeks oral bisphosphonates treatment within 10 years of the consent"}
• {"criterion_text":"- Prior treatment with more than a single dose of intravenous bisphosphonate within 10 years of the consent"}
• {"criterion_text":"- Prior treatment with more than one dose of denosumab within 1 year of the consent"}
• {"criterion_text":"- Recent (last 12 months) or current treatment likely to affect bone – this does not include inhaled or intermittent oral therapy with steroids for asthma (no more than three months of oral steroids in previous 12 months)"}
• {"criterion_text":"- Severe Hepatic impairment (AST ≥ 144U/L, ALT ≥ 165U/L, GGT ≥ 183 U/L)"}
• {"criterion_text":"- Renal impairment (GFR <60ml/min/m2; GFR in children will be assessed using the Bedside Schwartz equation) if treated with aliskiren-containing products."}
• {"criterion_text":"- Diabetes mellitus if treated with aliskiren-containing products"}
• {"criterion_text":"- Cardiac failure if treated with diuretics (excluding grade 1 according to the NYHA Functional Classification)"}
• {"criterion_text":"- Pregnancy or lactation"}

Primary endpoints

• {"endpoint_text":"- Percentage change in CTX from baseline to week 24","definition_or_measurement_approach":"Measured as percentage change in the bone resorption marker carboxy-terminal crosslink of type I collagen (CTX) from baseline to week 24."}

Secondary endpoints

• {"endpoint_text":"- Percentage change in CTX from baseline to week 8","definition_or_measurement_approach":"Measured as percentage change in CTX from baseline to week 8."}
• {"endpoint_text":"- Percentage change in TGFβ & P1NP from baseline to week 8 and w24","definition_or_measurement_approach":"Measured as percentage change in TGFβ and P1NP from baseline to week 8 and week 24."}
• {"endpoint_text":"- Change in DXA LSaBMD from baseline to w24","definition_or_measurement_approach":"Change from baseline to week 24 in lumbar spine areal bone mineral density (LSaBMD) by DXA."}
• {"endpoint_text":"- Change in radial and tibial total vBMD by HRpQCT from baseline to w24","definition_or_measurement_approach":"Change from baseline to week 24 in radial and tibial total volumetric BMD measured by high-resolution peripheral quantitative CT (HRpQCT)."}
• {"endpoint_text":"- Change in Timed Up and Go test from baseline to w24","definition_or_measurement_approach":"Change from baseline to week 24 in Timed Up and Go test performance (measure of muscle/functional mobility)."}
• {"endpoint_text":"- Change in QoL using OI-QOL & EQ-5D-5L-VAS from baseline to w24","definition_or_measurement_approach":"Change from baseline to week 24 in quality of life measured with the disease-specific OI-QOL instrument and the generic EQ-5D-5L with VAS."}

Italy

Earliest CTIS Part Ii Submission Date

13-02-2025

Latest Decision Or Authorization Date

13-03-2025

Processing Time Days

28

Number Of Sites

2

Number Of Participants

15

Primary sponsor

Full Name

Istituto Ortopedico Rizzoli

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy