Trial Outcomes & Findings for Oral Liquid 13-cis-retinoic Acid (13-CRA) (NCT NCT03291080)
NCT ID: NCT03291080
Last Updated: 2021-10-19
Results Overview
Relative bioavailability (Area under the curve) of 13-CRA administered as oral liquid (test) and extracted capsule (reference) formulations.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
20 participants
Primary outcome timeframe
On day 1 and 14 of treatment
Results posted on
2021-10-19
Participant Flow
Participant milestones
| Measure |
First Oral Liquid, Then Capsule
Oral liquid formulation of 13-Cis Retinoic Acid (test product) in the first cycle. Then extracted 13-CRA capsule (reference product) in the second cycle.
|
First Capsule, Then Oral Liquid
13-CRA capsules extracted per standard of care (reference product) in the first cycle. Then oral liquid formulation of 13-CRA (test product) in the second cycle.
|
|---|---|---|
|
First Cycle (2 Weeks)
STARTED
|
11
|
9
|
|
First Cycle (2 Weeks)
COMPLETED
|
11
|
9
|
|
First Cycle (2 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Washout (2 Weeks)
STARTED
|
11
|
9
|
|
Washout (2 Weeks)
COMPLETED
|
11
|
9
|
|
Washout (2 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Second Cylcle (2 Weeks)
STARTED
|
9
|
11
|
|
Second Cylcle (2 Weeks)
COMPLETED
|
8
|
11
|
|
Second Cylcle (2 Weeks)
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Oral Liquid 13-cis-retinoic Acid (13-CRA)
Baseline characteristics by cohort
| Measure |
Liquid First
n=11 Participants
Oral liquid formulation of 13-Cis Retinoic Acid (test product) administered in Cycle 1, then 13-CRA extracted capsules (reference product) administered in Cycle 2. The daily dose in each cycle was 200mg per m\^2 (in 2 divided doses), reduced to 160 mg per m\^2 if weight \< 12 kg
|
Extracted Capsule First
n=9 Participants
13-CRA extracted capsules (reference product) administered in Cycle 1, then oral liquid formulation of 13-Cis Retinoic Acid (test product) administered in Cycle 2. The daily dose in each cycle was 200mg per m\^2 (in 2 divided doses), reduced to 160 mg per m\^2 if weight \< 12 kg
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Asian or Asian British
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Height
|
0.974 Metre
STANDARD_DEVIATION 0.113 • n=5 Participants
|
1.062 Metre
STANDARD_DEVIATION 0.21 • n=7 Participants
|
1.009 Metre
STANDARD_DEVIATION 0.163 • n=5 Participants
|
|
Weight
|
14.66 Kg
STANDARD_DEVIATION 3.47 • n=5 Participants
|
18.96 Kg
STANDARD_DEVIATION 9.09 • n=7 Participants
|
16.3 Kg
STANDARD_DEVIATION 6.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: On day 1 and 14 of treatmentPopulation: Relative bioavailability - AUC (h.ng/mL)
Relative bioavailability (Area under the curve) of 13-CRA administered as oral liquid (test) and extracted capsule (reference) formulations.
Outcome measures
| Measure |
13-CRA Oral Liquid
n=20 Participants
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 Participants
Oral liquid formulation - reference product
|
|---|---|---|
|
Relative Bioavailability
|
10009.0 (h.ng/mL)
Standard Deviation 3672.97
|
6075.9 (h.ng/mL)
Standard Deviation 2090.66
|
SECONDARY outcome
Timeframe: On day 1 and 14 of treatmentPharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
Outcome measures
| Measure |
13-CRA Oral Liquid
n=20 Participants
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 Participants
Oral liquid formulation - reference product
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
1237.6 (ng/mL)
Standard Deviation 662.67
|
748.2 (ng/mL)
Standard Deviation 379.28
|
SECONDARY outcome
Timeframe: On day 1 and 14 of treatmentPharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation
Outcome measures
| Measure |
13-CRA Oral Liquid
n=20 Participants
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 Participants
Oral liquid formulation - reference product
|
|---|---|---|
|
Time to Maximum Concentration (Tmax)
|
3.2 (h)
Standard Deviation 0.76
|
3.0 (h)
Standard Deviation 0.76
|
SECONDARY outcome
Timeframe: On day 1 and 14 of treatmentPharmacokinetic parameter for 13 CRA extracted capsules versus oral liquid formulation- metabolite 4-oxo-13-cisRA
Outcome measures
| Measure |
13-CRA Oral Liquid
n=20 Participants
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 Participants
Oral liquid formulation - reference product
|
|---|---|---|
|
Area Under Plasma Concentration Time Curve (AUC) Metabolite
|
38462.3 (h*ng/mL)
Standard Deviation 18913.60
|
23312.7 (h*ng/mL)
Standard Deviation 10947.59
|
SECONDARY outcome
Timeframe: On day 1 and 14 of treatmentPharmacokinetic parameter for metabolite 4-oxo-13-cisRA PK
Outcome measures
| Measure |
13-CRA Oral Liquid
n=20 Participants
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 Participants
Oral liquid formulation - reference product
|
|---|---|---|
|
Cmax (ng/mL)- Metabolite
|
3366.2 (ng/mL)
Standard Deviation 1648.08
|
2039.1 (ng/mL)
Standard Deviation 952.23
|
SECONDARY outcome
Timeframe: On day 1 and 14 of treatmentT max for metabolite -4-oxo-13-cisRA PK
Outcome measures
| Measure |
13-CRA Oral Liquid
n=20 Participants
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 Participants
Oral liquid formulation - reference product
|
|---|---|---|
|
T Max of Metabolite
|
7.1 (h)
Standard Deviation 1.16
|
6.9 (h)
Standard Deviation 1.16
|
Adverse Events
13-CRA Oral Liquid
Serious events: 10 serious events
Other events: 18 other events
Deaths: 0 deaths
13-CRA Extracted Capsule
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
13-CRA Oral Liquid
n=20 participants at risk
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 participants at risk
Oral liquid formulation - reference product
|
|---|---|---|
|
Gastrointestinal disorders
Haematemesis
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Renal and urinary disorders
Acute Kidney Injury
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
|
Gastrointestinal disorders
vomiting
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
|
General disorders
Pyrexia
|
15.0%
3/20 • Number of events 5 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 3 • Through study completion, an average of 2 months.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
|
Infections and infestations
Pharyngitis
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Infections and infestations
Respiratory syncitial virus infection
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
|
Nervous system disorders
Enteric neuropathy
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
5.0%
1/20 • Number of events 1 • Through study completion, an average of 2 months.
|
Other adverse events
| Measure |
13-CRA Oral Liquid
n=20 participants at risk
Oral liquid formulation - test product
|
13-CRA Extracted Capsule
n=20 participants at risk
Oral liquid formulation - reference product
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
|
Eye disorders
Dry eye
|
15.0%
3/20 • Number of events 3 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
|
Gastrointestinal disorders
Chapped Lips
|
40.0%
8/20 • Number of events 9 • Through study completion, an average of 2 months.
|
30.0%
6/20 • Number of events 6 • Through study completion, an average of 2 months.
|
|
Gastrointestinal disorders
Constipation
|
15.0%
3/20 • Number of events 4 • Through study completion, an average of 2 months.
|
15.0%
3/20 • Number of events 3 • Through study completion, an average of 2 months.
|
|
Gastrointestinal disorders
Diarrhoea
|
30.0%
6/20 • Number of events 7 • Through study completion, an average of 2 months.
|
25.0%
5/20 • Number of events 6 • Through study completion, an average of 2 months.
|
|
Gastrointestinal disorders
Vomiting
|
15.0%
3/20 • Number of events 5 • Through study completion, an average of 2 months.
|
20.0%
4/20 • Number of events 5 • Through study completion, an average of 2 months.
|
|
General disorders
Pain
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
General disorders
Pyrexia
|
40.0%
8/20 • Number of events 10 • Through study completion, an average of 2 months.
|
30.0%
6/20 • Number of events 8 • Through study completion, an average of 2 months.
|
|
General disorders
Swelling face
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
|
Investigations
Platelet count decreased
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 3 • Through study completion, an average of 2 months.
|
|
Nervous system disorders
Headache
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
40.0%
8/20 • Number of events 8 • Through study completion, an average of 2 months.
|
50.0%
10/20 • Number of events 12 • Through study completion, an average of 2 months.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
35.0%
7/20 • Number of events 7 • Through study completion, an average of 2 months.
|
20.0%
4/20 • Number of events 4 • Through study completion, an average of 2 months.
|
|
Vascular disorders
Hypotension
|
0.00%
0/20 • Through study completion, an average of 2 months.
|
10.0%
2/20 • Number of events 2 • Through study completion, an average of 2 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place