Trial Outcomes & Findings for Bioequivalence Study of Two Different Formulations of N-acetyl-cysteine (NAC) (NCT NCT02265224)
NCT ID: NCT02265224
Last Updated: 2021-11-05
Results Overview
Cmax is the maximum concentration level of the drug reached in plasma.
COMPLETED
PHASE1
48 participants
0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
2021-11-05
Participant Flow
48 healthy subjects were included in the study, as planned, and received test and reference treatment according to the cross-over design.
Subjects were assigned to a sequence of treatments (TR or RT) according to the randomisation list. Randomisation number was given to the subjects on study day -1, Period 1, and was used to assign the treatment sequence according to the randomisation list. The randomisation list was computer-generated by the Contract Research Organisation (CRO) Biometry Unit, using the PLAN procedure of SAS® version 9.3 (TS1M1) (24). The randomisation list was supplied to the Phase I Unit before study start.
Participant milestones
| Measure |
Enrolled Subjects Set
According to the crossover design, all the enrolled subjects received both NAC formulations based on the randomization schedule.Two single doses of 600 mg of NAC (one with test and one with reference formulation) were administered to each volunteer in two subsequent study periods (morning of day 1), separated by a wash-out interval of at least 5 days.
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|---|---|
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Overall Study
STARTED
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48
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Overall Study
COMPLETED
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48
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioequivalence Study of Two Different Formulations of N-acetyl-cysteine (NAC)
Baseline characteristics by cohort
| Measure |
Enrolled Subjects Set
n=48 Participants
According to the crossover design, all the enrolled subjects received both NAC formulations based on the randomization schedule. Two single doses of 600 mg of NAC (one with test and one with reference formulation) were administered to each volunteer in two subsequent study periods (morning of day 1), separated by a wash-out interval of at least 5 days.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
|
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Age, Categorical
Between 18 and 65 years
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48 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
|
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Age, Continuous
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42.6 years
STANDARD_DEVIATION 8.6 • n=5 Participants
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Sex: Female, Male
Female
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25 Participants
n=5 Participants
|
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Sex: Female, Male
Male
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23 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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47 Participants
n=5 Participants
|
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Unknown or Not Reported
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1 Participants
n=5 Participants
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Region of Enrollment
Switzerland
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48 participants
n=5 Participants
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PRIMARY outcome
Timeframe: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
Cmax is the maximum concentration level of the drug reached in plasma.
Outcome measures
| Measure |
Test
n=48 Participants
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Reference
n=48 Participants
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Cmax of NAC After Single Dose Administration of Test and Reference
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2804.38 ng/mL
Standard Deviation 899.47
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3215.63 ng/mL
Standard Deviation 1382.02
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PRIMARY outcome
Timeframe: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
AUC0-t is the Area under the concentration-time curve from time zero to time t, calculated with the linear trapezoidal summation from time 0 to the last measurable data point.
Outcome measures
| Measure |
Test
n=48 Participants
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Reference
n=48 Participants
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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AUC0-t of NAC After Single Dose Administration of Test and Reference
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10637.87 ng/mL*h
Standard Deviation 3100.94
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11773.11 ng/mL*h
Standard Deviation 3775.43
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SECONDARY outcome
Timeframe: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
AUC0-∞ is the area under the concentration-time curve extrapolated to infinity, calculated, if feasible, as AUC0-t + Ct/λz, where Ct is the last measurable drug concentration.
Outcome measures
| Measure |
Test
n=48 Participants
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Reference
n=48 Participants
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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AUC0-∞ of NAC After Single Dose Administration of Test and Reference
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12586.17 ng/mL*h
Standard Deviation 3577.24
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13739.43 ng/mL*h
Standard Deviation 4190.59
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SECONDARY outcome
Timeframe: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)time to achieve the maximum concentration level of the drug in plasma.
Outcome measures
| Measure |
Test
n=48 Participants
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
|
Reference
n=48 Participants
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Tmax of NAC After Single Dose Administration of Test and Reference
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1.00 hours
Interval 0.5 to 3.0
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1.00 hours
Interval 0.25 to 3.0
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SECONDARY outcome
Timeframe: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
Half-life (t1/2) is the time to halve the plasma concentration level of the drug.
Outcome measures
| Measure |
Test
n=48 Participants
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Reference
n=48 Participants
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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t1/2 of NAC After Single Dose Administration of Test and Reference
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14.11 hours
Standard Deviation 4.16
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13.59 hours
Standard Deviation 2.69
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SECONDARY outcome
Timeframe: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
Lambda zeta is the terminal elimination rate constant. Individual estimate of the terminal elimination rate constant can be calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves.
Outcome measures
| Measure |
Test
n=48 Participants
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
|
Reference
n=48 Participants
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Lambda Zeta of NAC After Single Dose Administration of Test and Reference
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0.05 1/h
Standard Deviation 0.01
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0.05 1/h
Standard Deviation 0.01
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SECONDARY outcome
Timeframe: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal product intake and had evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
Frel is the relative bioavailability, calculated as ratio AUC0-t (test)/ AUC0-t (reference)
Outcome measures
| Measure |
Test
n=48 Participants
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Reference
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose). The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Frel of NAC After Single Dose Administration of Test and Reference
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92.82 percentage
Standard Deviation 18.05
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—
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Adverse Events
Test - Reference
Reference - Test
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Test - Reference
n=48 participants at risk
N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose) followed by NAC 600 mg film-coated tablet (single dose)
N-acetylcysteine: The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Reference - Test
n=48 participants at risk
N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose) followed by NAC 600 mg uncoated tablet (single dose)
N-acetylcysteine: The product was administered according to the randomisation list and cross-over design, with 150 mL of still mineral water under fasting conditions on study day 1 of periods 1 or 2 at 8:00±1 h.
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Nervous system disorders
Dizziness
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4.2%
2/48 • Number of events 2 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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0.00%
0/48 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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Nervous system disorders
Headache
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4.2%
2/48 • Number of events 2 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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0.00%
0/48 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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Gastrointestinal disorders
Nausea
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2.1%
1/48 • Number of events 1 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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2.1%
1/48 • Number of events 1 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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Gastrointestinal disorders
Abdominal discomfort
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0.00%
0/48 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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2.1%
1/48 • Number of events 1 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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Gastrointestinal disorders
Vomiting
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2.1%
1/48 • Number of events 1 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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0.00%
0/48 • From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place