Effects of Pazopanib on Hereditary Hemorrhagic Telangiectasia Related Epistaxis and Anemia (Paz)

Part B Inclusion Criteria (all of the following are necessary): * A definite or probable diagnosis of hereditary hemorrhagic telangiectasia (HHT): 1. Definite clinical HHT defined as having at least 3 of the following criteria: * Spontaneous and recurrent epistaxis. * Multiple telangiectasias at characteristic sites: lips, oral cavity, fingers, nose. * Visceral lesions: GI telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs. * A first degree relative with HHT according to these criteria. 2. OR a definite diagnosis of HHT based on a pathogenic genetic mutation for HHT. 3. OR probable HHT based on having 2 of the above criteria with high clinical suspicion of HHT. * Stable IV iron use and/or blood transfusions stable for 12 weeks prior to test product initiation. * Must agree not to undergo cautery of nasal telangiectasias or to start new therapies for HHT while on study. * Women of childbearing potential must agree to abstinence or to use an acceptable double method contraception until 4 weeks after drug termination. Pregnancy testing will be done throughout the trial. * Men are mandated to use condoms. * Capable of giving signed informed consent. * Able and willing to return for outpatient visits at the protocol specified intervals. * Able and willing to complete blood pressure monitoring at home. * Able and willing to complete daily patient reported outcome measurements at home. * Must meet all of the inclusion criteria for either: Severe Anemia Cohort: i. Anemia mainly due to HHT (in the judgment of the PI) with average Hgb \<10 g/dL regardless of gender (average of at least three measures during screening and run in). ii. Epistaxis averaging at least 5 min/week over the six-week baseline and is generally stable in the clinical judgement of the investigator. Severe Epistaxis Cohort: i. Anemia mainly due to HHT (in the judgment of the PI) with Hgb \<12 g/dL in women or \<13 g/dL in men (average of at least three measures during screening and run in). ii. Epistaxis averaging at least 20 min/week over the six-week baseline and is generally stable in the clinical judgement of the investigator. Part B Exclusion Criteria: * Participant 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 incompletely treated cerebral arterio-venous malformations (AVMs) or cerebral arteriovenous fistulas (AVFs) that are symptomatic or have high-risk features detected on either MRI/MRA or digital subtraction angiography. High-risk features include: microhemorrhage seen on MRI; feeding artery aneurysm, nidus aneurysm or venous outflow stenosis seen on MRA, CTA, or catheter angiography. Non-shunting vascular brain lesions such as capillary vascular malformations, telangiectasias, and cavernous malformations are not an exclusion criterion. (Note: MRI scan does not need to be repeated at screening if AVMs and AVFs were absent on a scan at age ≥18 years). * Currently has perfused pulmonary AVMs with feeding artery diameter ≥ 3mm. * Known significant bleeding sources other than nasal or gastrointestinal. * Systemic use of a potent VEGF inhibitor (e.g., direct inhibitors of VEGF-receptor signaling such as sunitinib) in the 4 weeks prior to enrollment. Systemic use of bevacizumab in the 6 weeks prior to enrollment due to its longer half-life. * Active and recent onset of clinically significant diarrhea. * Current or recent (in the last 5 years) malignancies (except non-melanoma skin cancers) * Participant has had major surgery (e.g. surgical ligation of an AVM) or trauma within 28 days or had minor surgical procedures (e.g. central venous access line removal) within 7 days prior to dosing, the latter representing a recent wound, fracture or ulcer * Participant has a planned surgery during periods of active treatment and 6 weeks of follow up; case by case evaluation if PI desires inclusion with medical monitor agreement. * Participant has clinically significant gastrointestinal abnormalities (other than hereditary hemorrhagic telangiectasia related vascular lesions). * Participant during the 6 months prior to first dose of study drug has a history of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, untreated deep vein thrombosis (DVT), myocardial infarction, or any other thrombotic event. * Presence of intrinsic heart disease as evidenced by any of the following: Echo derived left ventricular ejection fraction \< 45%; Unstable obstructive CAD; history of MI, CABG, or PCI in the last 6 months; Infiltrative and/or restrictive cardiomyopathies; Significant pericardial disease; or clinical heart failure with more than moderate mitral valve or aortic valve disease. In the absence of clinical heart failure, EKG abnormalities, or known cardiac functional disease (e.g., MI or cardiomyopathy), a previous echo during adulthood is adequate. If there is history for coronary disease or cardiomyopathy, an echo in the past 5 years will be adequate for screening. If the patient has current clinical heart failure, a recent cardiac event in last 5 yrs, or a cardiac event since the most recent echo, an echo in the past 6 months will be necessary for screening. Clinical heart failure due to liver AVM or anemia, and not associated with the above findings (with an EF \>=45%) will be eligible for enrollment. * Unable or unwilling to discontinue use of prohibited medications list in Section 6.5.2 for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the randomization and for the duration of the study. * The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the start of randomization: 4 weeks, 4 half-lives or the duration of the biological effect of the investigational product (whichever is longer). * QT corrected interval \>450 msec for men or \>460 msec for women, based on averaged QT corrected interval values of triplicate ECGs obtained over a brief recording period. * History of familial prolonged QT. * Any concomitant medication which is known to prolong QT. * Average baseline hemoglobin \<6 g/dL. * Platelets \< 75x10\^9 /L. * International normalized ratio (INR) \> 1.5x ULN or activated partial thromboplastin time (aPTT) \> 1.5x ULN (unless due to known concurrent medications, e.g. warfarin). * Alanine Transaminase (ALT) \>2 x upper limit of normal. * Bilirubin \>1.5x upper limit of normal (isolated bilirubin \>1.5x upper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin \< 35%). * Participant has poorly controlled hypertension \[defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg\]. If BP is poorly controlled at screen visit, initiation or adjustment of antihypertensive medication(s) is permitted during the run-in period prior to randomization. Prior to randomization, blood pressure must be assessed three times and the mean SBP/DBP must be \< 140/90 mmHg in order for a patient to be randomized. * Substantive renal disease (eGFR \<30 mL/min/1.73m2calculated using the Cockcroft-Gault formula) * Echo derived left ventricular ejection fraction \< 45%. * Thyroid stimulating hormone (TSH) \> 1.5 x upper limit of normal. * Urine protein to creatinine ratio \> 0.4. * Neutrophil count \<1000 /mm\^3. Part C Eligibility All patients who completed Part B will be eligible for Part C unless significant safety concerns have been raised. Participants must be able and willing to sign the Extension ICF. Neither the Study Doctor or the participant will be informed of which drug (active or placebo) received during Part B.