A Phase 1/2 interventional study of Liquid 13-Cis Retinoic Acid and Extracted capsules 13-CRA in Neuroblastoma, sponsored by Nova Laboratories Limited. Completed at 10 sites in United Kingdom. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2021-10-19.
Sponsored by Nova Laboratories Limited · Phase 1/2, Interventional, and Other
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.
All patients requiring at least two cycles of 13-CRA therapy will be eligible for recruitment into the trial.
13-CRA will be prescribed to patients according to local treatment protocols at each clinical site. The dose administered will be 200mg/m2/day for both test and reference product. Patients with a body weight of ≤12kg will receive a dose of 160 mg/m2/day.
The pharmacokinetics of 13-CRA liquid (test product) and extracted from capsule (reference product) will be evaluated over two months. Prior to the initiation of 13-CRA treatment as part of the trial, patients will be randomised to receive either liquid or capsule formulation in "My-CRA month 1". The patients will then cross-over to the alternative formulation in "My-CRA month 2". The patients on the trial who require further treatment will revert to standard therapy i.e. 13-CRA extracted from capsules according to local practice.
675 studies on the registry are indexed under Neuroblastoma; 127 are open to participants now.
This study's enrollment of 20 is below the median of 32 across 507 interventional studies indexed under Neuroblastoma.
Browse Neuroblastoma studies →Nova Laboratories Limited is the lead sponsor of 5 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Prior to each cycle:
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
Withdrawal Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Oral liquid formulation of 13-Cis Retinoic Acid - test product.
Drug: Liquid 13-Cis Retinoic Acid
Isotretinoin capsules (13-CRA extracted per standard of care)- reference product.
Drug: Extracted capsules 13-CRA
Liquid 13-Cis Retinoic Acid
Also known as: Isotretinoin
Extracted capsules 13-CRA
Also known as: Isotretinoin
Relative Bioavailability
Relative bioavailability (Area under the curve) of 13-CRA administered as oral liquid (test) and extracted capsule (reference) formulations.
Time frame: On day 1 and 14 of treatment
Maximum Plasma Concentration (Cmax)
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
Time frame: On day 1 and 14 of treatment
Time to Maximum Concentration (Tmax)
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
Time frame: On day 1 and 14 of treatment
Area Under Plasma Concentration Time Curve (AUC) Metabolite
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation- metabolite 4-oxo-13-cisRA
Time frame: On day 1 and 14 of treatment
Cmax (ng/mL)- Metabolite
Pharmacokinetic parameter for metabolite 4-oxo-13-cisRA PK
Time frame: On day 1 and 14 of treatment
T Max of Metabolite
T max for metabolite -4-oxo-13-cisRA PK
Time frame: On day 1 and 14 of treatment
| Milestone | First Oral Liquid, Then Capsule | First Capsule, Then Oral Liquid |
|---|---|---|
| Started | 11 | 9 |
| Completed | 11 | 9 |
| Not completed | 0 | 0 |
| Milestone | First Oral Liquid, Then Capsule | First Capsule, Then Oral Liquid |
|---|---|---|
| Started | 11 | 9 |
| Completed | 11 | 9 |
| Not completed | 0 | 0 |
| Milestone | First Oral Liquid, Then Capsule | First Capsule, Then Oral Liquid |
|---|---|---|
| Started | 9 | 11 |
| Completed | 8 | 11 |
| Not completed | 1 | 0 |
Relative bioavailability (Area under the curve) of 13-CRA administered as oral liquid (test) and extracted capsule (reference) formulations.
| (h.ng/mL) | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| Relative Bioavailability | 10009.0 ± 3672.97 | 6075.9 ± 2090.66 |
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
| (ng/mL) | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 1237.6 ± 662.67 | 748.2 ± 379.28 |
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
| (h) | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| Time to Maximum Concentration (Tmax) | 3.2 ± 0.76 | 3.0 ± 0.76 |
Pharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation- metabolite 4-oxo-13-cisRA
| (h*ng/mL) | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| Area Under Plasma Concentration Time Curve (AUC) Metabolite | 38462.3 ± 18913.60 | 23312.7 ± 10947.59 |
Pharmacokinetic parameter for metabolite 4-oxo-13-cisRA PK
| (ng/mL) | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| Cmax (ng/mL)- Metabolite | 3366.2 ± 1648.08 | 2039.1 ± 952.23 |
T max for metabolite -4-oxo-13-cisRA PK
| (h) | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| T Max of Metabolite | 7.1 ± 1.16 | 6.9 ± 1.16 |
Collected over Through study completion, an average of 2 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 13-CRA Oral Liquid | 0/20 (0%) | 10/20 (50%) | 18/20 (90%) |
| 13-CRA Extracted Capsule | 0/20 (0%) | 5/20 (25%) | 15/20 (75%) |
| Event | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| PyrexiaGeneral disorders | 3/20 | 2/20 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/20 | 2/20 |
| HaematemesisGastrointestinal disorders | 1/20 | 0/20 |
| Acute Kidney InjuryRenal and urinary disorders | 1/20 | 0/20 |
| DiarrhoeaGastrointestinal disorders | 1/20 | 1/20 |
| vomitingGastrointestinal disorders | 1/20 | 1/20 |
| HypersensitivityImmune system disorders | 0/20 | 1/20 |
| PharyngitisInfections and infestations | 1/20 | 0/20 |
| Respiratory syncitial virus infectionInfections and infestations | 0/20 | 1/20 |
| Enteric neuropathyNervous system disorders | 1/20 | 0/20 |
| Event | 13-CRA Oral Liquid | 13-CRA Extracted Capsule |
|---|---|---|
| Dry SkinSkin and subcutaneous tissue disorders | 8/20 | 10/20 |
| Chapped LipsGastrointestinal disorders | 8/20 | 6/20 |
| PyrexiaGeneral disorders | 8/20 | 6/20 |
| Skin exfoliationSkin and subcutaneous tissue disorders | 7/20 | 4/20 |
| DiarrhoeaGastrointestinal disorders | 6/20 | 5/20 |
| VomitingGastrointestinal disorders | 3/20 | 4/20 |
| Dry eyeEye disorders | 3/20 | 2/20 |
| ConstipationGastrointestinal disorders | 3/20 | 3/20 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/20 | 2/20 |
| PainGeneral disorders | 2/20 | 0/20 |
| Age, Categorical(Participants) | Liquid First | Extracted Capsule First | Total |
|---|---|---|---|
| <=18 years | 11 | 9 | 20 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Liquid First | Extracted Capsule First | Total |
|---|---|---|---|
| Female | 4 | 1 | 5 |
| Male | 7 | 8 | 15 |
| Race/Ethnicity, Customized(Participants) | Liquid First | Extracted Capsule First | Total |
|---|---|---|---|
| Race — White | 8 | 7 | 15 |
| Race — Asian or Asian British | 2 | 2 | 4 |
| Race — Other | 1 | 0 | 1 |
| Height(Metre) | Liquid First | Extracted Capsule First | Total |
|---|---|---|---|
| Mean | 0.974 ± 0.113 | 1.062 ± 0.21 | 1.009 ± 0.163 |
| Weight(Kg) | Liquid First | Extracted Capsule First | Total |
|---|---|---|---|
| Mean | 14.66 ± 3.47 | 18.96 ± 9.09 | 16.3 ± 6.5 |
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drug tested here: Isotretinoin
Nova Laboratories Limited