Evaluation of Pazopanib on Bleeding in Subjects With Hereditary Haemorrhagic Telangiectasia

Inclusion Criteria: * Males/females aged between 18 and 75 years of age inclusive, at the time of signing the informed consent. * Diagnosis of definite or possible HHT by the Curaçao criteria. According to the Curaçao criteria, a definite diagnosis of HHT is defined as having at least 3 of the following criteria while a possible diagnosis is defined as 2 criteria: a) spontaneous and recurrent epistaxis; b) multiple telangiectasias at characteristic sites: lips, oral cavity, fingers, nose; c) visceral lesions: gastrointestinal (GI) telangiectasia, pulmonary, hepatic, cerebral or spinal arteriovenous malformations (AVMs); d) a first degree relative with HHT according to these criteria. * Subject meets at least one of the following criteria: a) Severe epistaxis over previous 4 weeks defined as an average of at least 3 nose bleeds per week AND a total duration of greater than 15 min per week AND requiring iron therapy (oral and/or intravenous); b) Moderate or severe iron deficiency anaemia (Hgb \< 11gram \[g\]/deciliter \[dL\], at screening) despite iron infusions (at least 0.5g iron per month) or blood transfusions (at least 2 units per month) AND substantial compromise in the quality of life according to the investigator (e.g. nose bleeds, lethargic, cannot maintain job, listless, fatigue). Anaemia must be HHT related in the opinion of the investigator, ie: due to HHT-defined bleeding (epistaxis and/or bleeding from the GI tract \[presence of telangiectatic lesions, exclusion of active ulcer disease or other infection, inflammation\]), and lack of other known etiologies such as blood dyscrasias. * Epistaxis (if applicable) is considered to be clinically stable during the 4 weeks prior to Screening in the clinical judgment of the investigator (i.e. no major changes in frequency or duration of epistaxis). * 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 \[for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhoea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 milli-international units per milliliter (MIU/mL) and estradiol \< 40 picogram per milliliter (pg/mL) (\<147 picomole per liter \[pmol/L\]) is confirmatory\]. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Subject is able and willing to return for outpatient visits at the protocol specified intervals. * Subject agrees not to undergo laser ablation of nasal telangiectasias or take any experimental therapies for HHT other than the study drug while participating in the study (over the counter medications, topical treatments, nasal hygiene and palliative therapies are acceptable as long as use is consistent). If subjects stop taking experimental therapies on entry to the study there should be a wash-out period of at least 5 half-lives prior to the start of the run-in). * Based on averaged corrected QT either Bazett's formula (QTcB), Fridericia's formula (QTcF) values of triplicate ECGs obtained over a brief recording period: QTc \< 450 milliseconds (msec); or QTc \< 480 msec in subjects with Bundle Branch Block. Exclusion Criteria: * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones; and with the exception of vascular abnormalities that are related to the HHT). * Subject has known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib that in the opinion of the investigator contradicts their participation. * Currently has untreated cerebral vascular malformations (CVMs) (Note: magnetic resonance imaging \[MRI\] scan does not need to be repeated at Screen if CVMs were absent on scan after age 18 years or in the last 5 years). * Currently has known pulmonary AVMs with feeding artery diameter \>3 millimeter (mm). * Symptomatic liver AVMs (defined as chronic right upper quadrant pain, symptomatic portal hypertension or heart failure). * Known significant bleeding sources other than nasal or gastrointestinal. * Systemic use of a vascular endothelial growth factor (VEGF) inhibitor in the past 12 weeks or previous enrolment in this study. * Current use of anticoagulants including but not limited to vitamin K antagonists (e.g., warfarin) at any dose; unfractionated or low molecular weight heparins at standard doses for treatment of venous thromboembolism (VTE) (e.g., enoxoparin); antiplatelets (e.g., clopidogrel), or direct factor Xa inhibitors (e.g., apixaban). Use of low dose aspirin \<= 81mg is allowed as long as use is consistent. * Active and recent onset diarrhoea. * Current or recent malignancies (except non-melanoma skin cancers) Subject has: a) had major surgery (eg, surgical ligation of an AVM) or trauma within 28 days; b) had minor surgical procedures (eg, central venous access line removal) within 7 days prior to dosing; c) any non-healing wound, fracture or ulcer * Subject has clinically significant gastrointestinal abnormalities (other than HHT-related vascular lesions) including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug (eg, short bowel syndrome), active peptic ulcer, known intraluminal metastatic lesions/s with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other gastrointestinal conditions with increased risk of perforation, lifetime history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess * Subject has a history of cerebrovascular accident (including transient ischaemic attacks), pulmonary embolism or untreated deep vein thrombosis (DVT) within the 6 months prior to first dose of study drug. * Subject has a history of any one or more of the following cardiovascular conditions within the 6 months prior to first dose of study drug: cardiac angioplasty or stenting, myocardial infarction, unstable angina, ischaemic stroke, symptomatic peripheral vascular disease * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA). * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. * Hgb \< 7 gram per deciliter (g/dL). * Platelets \< 100x10\^9/L, International normalized ratio (INR) \> 1.2x upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) \>1.2xULN. * Alanine aminotransferese (ALT) \>= 2xULN or bilirubin \> 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). Subject has poorly controlled hypertension \[defined as systolic blood pressure (SBP) \>= 140 millimeter of mercury (mmHg) or diastolic blood pressure (DBP) \>= 90mmHg\]. Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. At Screening, blood pressure must be assessed three times and the mean SBP/DBP must be \<140/90 mmHg in order for a subject to be eligible for the study. * Substantive renal disease (estimated glomerular filtration rate \[eGFR\] \< 60 mL/minute/1.73 meter\^3 calculated using the Cockcroft-Gault formula) * Thyroid stimulating hormone \> ULN. * Urine protein creatinine ratio \>0.3 * White blood cell count\< 3500/mm\^3. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the start of the run-in period: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Unable or unwilling to discontinue use of prohibited medications mentioned below for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the start of the run-in period and for the duration of the study. Medications that inhibit Cytochrome P450 3A4 (CYP3A4) may result in increased plasma pazopanib concentrations; therefore, co-administration of strong CYP3A4 inhibitors is PROHIBITED beginning 14 days prior to the first dose of study treatment until 15 days after the last dose of pazopanib. Strong CYP3A4 inhibitors include (but are not limited to): Antibiotics: clarithromycin, telithromycin, troleandomycin; human immunodeficiency virus (HIV): protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir); Antifungals: itraconzaole, ketoconazole, voriconazole, fluconazole; Antidepressants: nefazodone, Miscellaneous: grapefruit, grapefruit juice or other grapefruit product. statins, anticoagulants and tamoxifen use is prohibited.