Oral Liquid 13-cis-retinoic Acid (13-CRA)
My-CRA
Relative Bioavailability and Comparative Pharmacokinetics of 13-CRA Oral Liquid and Extracted Capsule Formulations: a Randomised, Open Label, Multi-dose, Cross-over Clinical Trial in Patients Requiring Treatment Cycles of 13-CRA.
1 other identifier
interventional
20
1 country
10
Brief Summary
An open label, randomised, multiple dose, cross-over relative bioavailability and pharmacokinetics trial of a novel oral liquid and capsule formulations of 13-CRA administered to patients from 0 months - \< 21 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Apr 2018
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 19, 2017
CompletedFirst Posted
Study publicly available on registry
September 25, 2017
CompletedStudy Start
First participant enrolled
April 17, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 12, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
September 12, 2019
CompletedResults Posted
Study results publicly available
October 19, 2021
CompletedOctober 19, 2021
September 1, 2021
1.4 years
July 19, 2017
May 27, 2021
September 22, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Relative Bioavailability
Relative bioavailability (Area under the curve) of 13-CRA administered as oral liquid (test) and extracted capsule (reference) formulations.
On day 1 and 14 of treatment
Secondary Outcomes (5)
Maximum Plasma Concentration (Cmax)
On day 1 and 14 of treatment
Time to Maximum Concentration (Tmax)
On day 1 and 14 of treatment
Area Under Plasma Concentration Time Curve (AUC) Metabolite
On day 1 and 14 of treatment
Cmax (ng/mL)- Metabolite
On day 1 and 14 of treatment
T Max of Metabolite
On day 1 and 14 of treatment
Study Arms (2)
Liquid
EXPERIMENTALOral liquid formulation of 13-Cis Retinoic Acid - test product.
Capsule
EXPERIMENTALIsotretinoin capsules (13-CRA extracted per standard of care)- reference product.
Interventions
Eligibility Criteria
You may qualify if:
- Male or female aged from 0 years to \< 21 years of age.
- Patient with high risk neuroblastoma, or unresectable, unfavourable histology intermediate risk neuroblastoma the latter age ≥ 18 months at diagnosis
- Patient who is scheduled to receive at least two treatment cycles of 13-CRA.
- Patient who cannot swallow 13-CRA capsules (i.e. requires extraction of 13-CRA from the capsules).
- Negative pregnancy test for females of child-bearing potential before initiation of treatment, and sexually active patients and partners agreeing to undertake adequate contraceptive measures (see section 4.5).
- Provision of a single or double lumen central venous catheter for sampling (i.e. already in place).
- Parent(s)/legal guardian able and willing to provide written informed consent for the patient to take part in the trial.
- Where applicable, the patient should assent to undergo blood sampling for pharmacokinetic purposes and to allow physiological measurements to be made.
You may not qualify if:
- Any clinically significant medical condition or abnormality, which, in the opinion of the investigator, might compromise the safety of the patient or which might interfere with the trial.
- Diagnosis of high-risk neuroblastoma (HRNBL) which is currently being treated on the SIOPEN HRNBL trial (patients who have exited this trial will be eligible).
- Known allergy to 13-CRA or any of the excipients.
- Inadequate contraception measures in females of childbearing age.
- Receiving concomitant treatment with tetracyclines.
- Prior to each cycle:
- Total bilirubin ≤ 1.5 x normal, and (SGPT) ALT ≤ 5 x normal. Veno-occlusive disease if present, should be stable or improving.
- Skin toxicity no greater than CTCAE Grade 1(10)
- Serum triglycerides \<5.65mmol/L.
- No haematuria and / or proteinuria on urinalysis.
- Serum calcium ≤ 2.9mmol/L.
- Serum creatinine based on age / gender as follows:
- Age Maximum Serum Creatinine µmol/L Male Female 1 month to \< 6 months 35 35 6 months to \< 1 year 44 44 1 to \< 2 years 53 53 2 to \< 6 years 70 70 6 to \< 10 years 88 88 10 to \< 13 years 106 106 13 to \< 16 years 132 124
- ≥ 16 years 150 124
- Patients with a seizure disorder must be well controlled and taking anticonvulsants. CNS toxicity \< grade 2 (CTCAE).
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Bruce Morland
Birmingham, United Kingdom
Dr Antony Ng
Bristol, United Kingdom
Dr Amos Burke
Cambridge, United Kingdom
Mark Brougham
Edinburgh, United Kingdom
Dr Martin Elliott
Leeds, United Kingdom
Dr Guiseppe Barone
London, United Kingdom
Dr Guy Makin
Manchester, United Kingdom
Dr Madhumita Dandapani
Nottingham, United Kingdom
Kate Wheeler
Oxford, United Kingdom
Sucheta Vaidya
Sutton, United Kingdom
Related Publications (1)
Veal GJ, Tweddle DA, Visser J, Errington J, Buck H, Marange J, Moss J, Joseph S, Mulla H. Pharmacokinetics and Safety of a Novel Oral Liquid Formulation of 13-cis Retinoic Acid in Children with Neuroblastoma: A Randomized Crossover Clinical Trial. Cancers (Basel). 2021 Apr 14;13(8):1868. doi: 10.3390/cancers13081868.
PMID: 33919763DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr Hussain Mulla
- Organization
- Nova Laboratories
Study Officials
- STUDY DIRECTOR
Hussain Mulla, PhD
Nova Laboratories Limited
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 19, 2017
First Posted
September 25, 2017
Study Start
April 17, 2018
Primary Completion
September 12, 2019
Study Completion
September 12, 2019
Last Updated
October 19, 2021
Results First Posted
October 19, 2021
Record last verified: 2021-09
Data Sharing
- IPD Sharing
- Will not share