Ignite Creation Date:
2024-05-06 @ 9:15 AM
Last Modification Date:
2024-10-26 @ 12:12 PM
Study NCT ID:
NCT02939547
Status:
COMPLETED
Last Update Posted:
2021-02-21
First Post:
2016-09-21
Brief Title:
Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 NPC1
Sponsor:
Cyclo Therapeutics Inc
Organization:
Cyclo Therapeutics Inc
Study Overview
Official Title:
A Phase I Study to Evaluate the Single and Multiple-dose Pharmacokinetics of Intravenous Trappsol Cyclo HP-Beta-CD in Patients With Niemann-Pick Disease Type C NPC-1 and the Effects of Dosing Upon Biomarkers of NPC Disease
Status:
COMPLETED
Status Verified Date:
2021-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 monthsPatients 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 A samples of cerebrospinal fluid CSF will be taken by lumbar puncture during the first treatment dose and may be collected during subsequent 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 treatmentThis study is being sponsored and funded by CTD holdings Inc It is planned to be run in the USA
Detailed Description:
The planned study has been designed as a Phase I double-blind randomised multi-centre parallel group study based on information and data available from the administration of Trappsol Cyclo via compassionatenamed 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 11 to one of the two dose levels 1500 mgkg or 2500 mgkg six patients per dose level Treatment will be administered every two weeks by slow IV infusion over 8 to 9 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 mgkg 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 metabolismturnover 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
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 11 to one of the two dose levels 1500 mgkg or 2500 mgkg six patients per dose level Treatment will be administered every two weeks by slow IV infusion over 8 to 9 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 mgkg 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 metabolismturnover 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None