Study of safety and tolerability following administration of metformin in patients with idiopathic pulmonary fibrosis (IPF)

Prior treatment

• Current / previous exacerbation / respiratory infection within the last four weeks
• Previous episode of lactic acidosis and any type of acute metabolic acidosis
• Concurrent participation in another clinical trial with an experimental treatment
• Previous participation in other clinical trials involving other investigational medicinal products whose toxicity overlaps (or could overlap) with that of the investigational medicinal product and its relevant metabolites within five times the half-life of the medicinal product or the metabolites (whichever is longer), in order to avoid toxicity
• Concomitant emphysema > 10% of lung volume (by High Resolution Computed Tomography (HRCT))
• Concomitant medication with OCT1-inhibitors (except for therapy with nintedanib) and inducers, as well as OCT2-inhibitors.
• Concomitant COPD with FEV1/FVC ratios < 70%
• Concomitant malignant disease requiring therapy

Other illness

• Diabetes mellitus type I or II
• History of alcohol or drug abuse in the past year and alcohol consume during the clinical trial
• Acute conditions that can lead to impaired kidney function, e.g., dehydration, severe infections, shock.
• Diseases (especially acute diseases or worsening chronic diseases) that can lead to tissue hypoxia, such as decompensated heart failure, recent myocardial infarction, shock, worsening of respiratory failure during the last 4 weeks.
• Any other liver disease with elevated ART/ARS >3 times the upper normal limit (UNL)

Lab values

• Hypersensitivity to the active substance or other ingredients like: Povidone K30, highly dispersed silicon dioxide, Magnesium stearate, Hypromellose, Titanium dioxide, Macrogol 400, Lactose, cellulose powder, microcrystalline cellulose, red iron oxide.
• Hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption
• Renal insufficiency (GFR < 60% predicted and/or Creatinine > 2mg/dl)
• Any acute / chronic heart failure with ejection fraction of < 40%

Other

• Any NSTEMI or STEMI within the last 4 weeks
• Patients with known bronchial asthma
• Assessment by the investigator that the patient should not participate in the study if the patient is unlikely to be able to comply with the study procedures, limitations and requirements
• Contrast agents within 48h
• Pregnant or breastfeeding women
• Estimated life expectancy of less than 1 year for any reason
• Chronic liver cirrhosis > Child A

• Patient (female or male) must be > 40 years old
• For WOCBP: A negative result in highly sensitive pregnancy test.
• Willingness of women of childbearing potential (WOCBP) to use acceptable effective methods of contraception* during treatment and until treatment discontinuation.
• Definite IPF according to ATS/ERS Consensus Guidelines
• Forced Vital Capacity (FVC) > 50% predicted
• Diffusion Capacity for CO (TLCO) > 25% predicted
• pO2 > 60 mm Hg at rest, with no more than 2l/min oxygen flow at maximum
• pO2 > 60 mm Hg under exercise, with no more than 6l/min oxygen flow at maximum
• Patients treated with standard of care (including Nerandomilast) for more than 3 months or who failed standard of care and who are off therapy at least 4 weeks
• Signed written informed consent
• Ability and willingness to comply with study procedures