Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1)

2016-10-21 04:08:21 | BioPortfolio


This research study is being conducted to find out whether Trappsol® Cyclo™, an experimental treatment for people with Niemann Pick disease Type C (NPC-1) is safe at 2 different dose levels and what effects it has on people who have this condition. NPC-1 is caused by a defect in the protein which is important for the transport of fatty substances like cholesterol out of cells. Without this protein, fats build up in the cells ultimately leading to organ damage. The way in which this experimental treatment works is not fully understood but laboratory experiments have shown that it can potentially remove cholesterol build up from the cells in people who have NPC-1. Approximately 12 patients will be asked to take part in this research study for up to 20 weeks (w) in total (including screening. treatment and follow-up). Recruitment is expected to take 6- 9 months.Patients who take part will receive treatment by an intravenous infusion every two weeks. The study will look at what the body does to the drug as well as what the drug does to the body by taking and examining blood and urine samples. Samples of cerebrospinal fluid (CSF) will be taken by lumbar puncture during and following the first and subsequent treatment doses. Liver and skin biopsy specimens will be taken to assess filipin staining. Cholesterol metabolism will be investigated in liver samples and splenic and hepatic elasticity will be assessed by ultrasound..Patients will also have their hearing tested, be asked questions by their doctor as well completing questionnaires to help assess any changes in their condition during treatment.This study is being sponsored and funded by CTD holdings Inc. It is planned to be run in the USA,.


The planned study has been designed as a Phase I, double-blind, randomised, single-centre, parallel group study based on information and data available from the administration of Trappsol Cyclo via compassionate/named patient use in patients with NPC-1, and data on other cyclodextrin products in the scientific literature.

The study is comprised of a screening phase of up to 4w a treatment phase of 12w and a 4w follow-up The primary objective is to compare the plasma pharmacokinetics of single and multiple doses of two different levels of IV Trappsol Cyclo .Secondary objectives include investigation of the HP-β-CD effect of different doses of IV Trappsol Cyclo upon serum and lymphocytic markers of cholesterol metabolism and evaluation of Trappsol concentrations in the cerebrospinal fluid (CSF) following IV administration , evaluation of the impact of treatment upon measures of neurological function including ataxia, aphasia and saccadic eye movements, and the impact of treatment upon behavioral aspects of NPC-1.

It is planned to recruit a total of 12 patients to the study. Patients will be randomised 1:1 to one of the two dose levels (1500 mg/kg or 2500 mg/kg; six patients per dose level). Treatment will be administered every two weeks by slow IV infusion over 8 hours at different concentrations to achieve the proscribed dose levels. Patients will receive treatment for a total of 12 weeks. Patients who withdraw prior to completion of the initial pharmacokinetic and pharmacodynamic assessments will be replaced.

The design of the proposed study thus enables early assessment of potential biochemical markers of response but allows for a sufficient dosing duration to enable the short-term effectiveness of Trappsol in NPC to be assessed.

The maximum dose proposed for this study is below the maximum dose for which long term clinical data is available in 2 patients (2800 mg/kg weekly for 3-5 years). Although individual clinicians have not always utilized an escalating rate of infusion, the reports of infusion related reactions in three patients suggest that this is an appropriate clinical strategy to mitigate the risk of such events and is consistent with dosing administration for other therapeutic agents. In the proposed study, treatment will be administered less frequently than has been undertaken in compassionate use. This longer dosing interval is supported by nonclinical data comparing the metabolism of cholesterol in non-human species with that in man; although a once weekly dosing interval was initially studied in man based on data in the mouse, HP-β-CD cholesterol metabolism/turnover in the mouse is 13-fold higher than in man which, in NPC, likely translates into a 13-fold slower accumulation of cholesterol in human cells compared with those of the mouse.Therefore, it is theorized that, given the slower cholesterol metabolism in humans, the dosing interval could be much less frequent in man than in mouse; however, based on what is known about cholesterol metabolism in humans and the pharmacokinetic and pharmacodynamic effect of HP-β-CD in the mouse, a dosing interval of 2 weeks in man is likely to be well within the therapeutic dosing interval and also minimizes the amount of infusions required to be administered.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science


Niemann-Pick Disease, Type C1




Not yet recruiting


CTD Holdings, Inc.

Results (where available)

View Results


Published on BioPortfolio: 2016-10-21T04:08:21-0400

Clinical Trials [1285 Associated Clinical Trials listed on BioPortfolio]

Study of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to Treat Niemann-Pick Type C1 (NPC1) Disease

This study evaluates the efficacy and safety of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in patients with neurologic manifestations of Niemann-Pick Type C1 (NPC1) Disease. Approximately ...

Safety and Tolerability Study of VTS-270 in Pediatric Participants With Niemann-Pick Type C (NPC) Disease

This is a Phase-2, multicenter, multiple dose, open-label, 2-part evaluation study which will primarily assess the safety and tolerability of VTS-270 (2-hydroxypropyl beta-cyclodextrin [HP...

Study of IV VTS-270 for Infantile Liver Disease Associated With Niemann-Pick Disease, Type C

Niemann-Pick disease, type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. NPC results ...

Open‐Label Study of Long‐Term Safety and Efficacy of Intravenous Trappsol Cyclo (HPβCD) in Niemann‐Pick Disease Type C

The purpose of this study is to provide continued access to treatment for NPC-1 after participation and completion of the Phase I trial CTD-TCNPC-101, when administered at doses of 1500 mg...

Open-label Study of VTS-270 in Participants With Neurologic Manifestations of Niemann-Pick Type C1

This is a multicenter, multinational, open-label study of to evaluate the long-term safety, tolerability, and efficacy of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in participants transiti...

PubMed Articles [22761 Associated PubMed Articles listed on BioPortfolio]

Niemann-Pick disease type C presenting as very early onset inflammatory bowel disease.

Niemann-Pick disease type C (NPC) has been reported in association with inflammatory bowel disease. In cases where colitis has been reported in association with NPC, the neurological manifestations of...

Niemann-Pick disease type C caused by NPC1 mutation in a case.

To delineate the clinical and genetic features of a Chinese boy suspected for Niemann-Pick disease type C.

Preliminary development of proxy-rated quality-of-life scales for children and adults with Niemann-Pick type C.

Niemann-Pick disease type C (NPC) is a rare life-limiting disease for which there is no cure. No scales currently exist to measure the impact of medication, physical therapy or clinical trials. The ai...

Generation of an induced pluripotent stem cell line (TRNDi004-I) from a Niemann-Pick disease type B patient carrying a heterozygous mutation of p.L43_A44delLA in the SMPD1 gene.

Niemann-Pick disease type B (NPB) is a rare autosomal recessive lysosomal storage disease caused by mutations in the SMPD1 gene, which encodes for acid sphingomyelinase. A human induced pluripotent st...

Sleep disorders in NiemannPick disease type C, beyond cataplexy.

The aim of this study was to clinically characterize sleep disorders in a cohort of Niemann-Pick type C (NPC) patients, correlating these findings with disease features and polysomnographic (PSG) resu...

Medical and Biotech [MESH] Definitions

An allelic disorder of TYPE A NIEMANN-PICK DISEASE, a late-onset form. It is also caused by mutation in SPHINGOMYELIN PHOSPHODIESTERASE but clinical signs involve only visceral organs (non-neuropathic type).

Derivative of beta-cyclodextrin that is used as an excipient for steroid drugs and as a lipid chelator.

The classic infantile form of Niemann-Pick Disease, caused by mutation in SPHINGOMYELIN PHOSPHODIESTERASE. It is characterized by accumulation of SPHINGOMYELINS in the cells of the MONONUCLEAR PHAGOCYTE SYSTEM and other cell throughout the body leading to cell death. Clinical signs include JAUNDICE, hepatosplenomegaly, and severe brain damage.

An autosomal recessive lipid storage disorder that is characterized by accumulation of CHOLESTEROL and SPHINGOMYELINS in cells of the VISCERA and the CENTRAL NERVOUS SYSTEM. Type C (or C1) and type D are allelic disorders caused by mutation of gene (NPC1) encoding a protein that mediate intracellular cholesterol transport from lysosomes. Clinical signs include hepatosplenomegaly and chronic neurological symptoms. Type D is a variant in people with a Nova Scotia ancestry.

An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC

More From BioPortfolio on "Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1)"

Quick Search

Relevant Topics

Statins (or HMG-CoA reductase inhibitors) are a class of drug used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been as...

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Trial