Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1

Exclusion Criteria

• •1. Aged below 18 or above 60 years of age at enrollment in the trial.
• •2. Severe manifestations of NPC1 that would interfere with the patient s ability to comply with the requirements of this protocol.
• •3. Neurologically asymptomatic patients.
• •4. Patients who have received any form of cyclodextrin or an HDACi in an attempt to treat NPC1.
• •5. History of hypersensitivity reactions to Vorinostat or components of the formulation.
• •6. Pregnancy or breastfeeding at any time during the study.
• •7. Patients with suspected infection of the CNS or any systemic infection.
• •8. Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1,500 per microliter.
• •9. Thrombocytopenia defined as a platelet count less than 75,000 per microliter, or a history of greater than or equal to grade 2 thrombocytopenia (50,000-75,000 platelets/microliter).
• •10. Prior use of anticoagulants or history/presence of a bleeding disorder.
• •11. Hepatic laboratory parameters (aspartate aminotransferase (AST), alanine aminotransferase, (ALT)) greater than four-times upper limit of normal.
• •12. Presence of anemia defined as two standard deviations below normal for age and gender.
• •13. Serum creatinine level greater than 1.5 times the upper limit of normal.
• •15. Proteinuria (1+ protein on urinalysis) Patient will not be excluded if urine protein/creatinine ratio is normal or if classified as benign by either patient's primary medical provider or upon obtaining a nephrology consult.
• •16. Serum potassium or Magnesium outside of the normal laboratory range prior to initiation of vorinostat therapy.
• •17. Diabetes or a fasting glucose greater than 106 mg/dl.
• •18. Active pulmonary disease, oxygen requirement or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
• •19. Patients with uncontrolled seizures per either of the criteria below.
• •1. Unstable frequency, type or duration of seizures. Quantified by a seizure log over the two months prior to enrollment.
• •2. Patients requiring antiepileptic medication changes (other than dose adjustments for weight) in the two months prior to enrollment, or requiring three or more antiepileptic medications to control seizures.
• •20. Use of another HDAC inhibitor or compounds with established HDAC inhibitory activity, including valproic acid, unless discontinued at least 2 months prior to enrollment.
• •21. History of a thromboembolic event (such as DVT or Pulmonary embolism).
• •22. Patients, who in the opinion of the investigators, are unable to comply with the protocol or have specific health concerns that would potentially increase the risk of participation.