no ConditionPhase 1NCT02265224

Bioequivalence Study of Two Different Formulations of N-acetyl-cysteine (NAC)

A Phase 1 study testing N-acetylcysteine in people with no Condition, run by Zambon SpA.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

Study primary Objective: To evaluate the bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of N-acetyl-cysteine 600 mg uncoated tablets vs. N-acetyl-cysteine 600 mg film-coated tablets (NAC) in healthy male and female volunteers. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: no Condition
What is being tested?: N-acetylcysteine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: No sites listed yet
Study dates: Sep 2014to Sep 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Informed consent: signed written informed consent before inclusion in the study
Sex and age: males and females,18-55 years old, inclusive
Body Mass Index (BMI): 18.5-30 kg/m2, inclusive
Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min of rest in the sitting position
Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
Contraception and fertility (females only): females of child-bearing potential and with an active sexual life must be using at least one of the following reliable methods of contraception:

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Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
A male sexual partner who agrees to use a male condom with spermicide
A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted.
For all female subjects, pregnancy test result must be negative at screening (serum β-HCG test) and day -1 (urine test).

Who cannot join

Electrocardiogram (ECG 12-leads, supine position): clinically significant abnormalities
Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study
Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study
Medications: medications, including over the counter (OTC) medications and herbal remedies for 2 weeks before the start of the study. Hormonal contraceptives for females will be allowed

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Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
Blood donation: blood donations for 3 months before this study
Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2010], caffeine (>5 cups coffee/tea/day) or tobacco abuse (≥6 cigarettes/day)
Drug test: positive result at the drug test at screening or day-1
Alcohol test: positive alcohol breath test at day -1
Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women

About this study

Official title: Comparative Bioavailability Study of N-acetyl-cysteine (NAC) 600 mg Uncoated Tablets vs. NAC 600 mg Film-coated Tablets in Healthy Male and Female Volunteers

Study primary Objective:

To evaluate the bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of N-acetyl-cysteine 600 mg uncoated tablets vs. N-acetyl-cysteine 600 mg film-coated tablets (NAC) in healthy male and female volunteers.

Study secondary objectives:

To describe the pharmacokinetic (PK) profile of NAC in plasma after single dose administration of NAC 600 mg uncoated tablets vs. NAC 600 mg film-coated tablets;
to collect safety and tolerability data after single dose administration of NAC 600 mg uncoated tablets vs. NAC 600 mg film-coated tablets.

Read the detailed description

This is single centre, single dose, open, randomised, cross-over, two-stage bioequivalence study to compare two different oral formulations of NAC.

The study has been conducted in healthy volunteers of both genders, in one single dose of both formulations.

The initial 48 subjects were sufficient to satisfy the study objectives on the basis of the ad interim preliminary bioequivalence test. The study was then considered as concluded and the second stage did not take place.

Conditions: no Condition
Being tested: N-acetylcysteine
Keywords: healthy volunteers

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-acetylcysteineDrug
Also called Fluimucil uncoated tablets
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.

Study groups in NCT02265224
Study group	Role	What they receive
Test - Reference	Experimental	N-acetylcysteine (NAC) 600 mg uncoated tablet (single dose) followed by NAC 600 mg film-coated tablet (single dose) Receives: Drug: N-acetylcysteine
Reference - Test	Active comparator	N-acetylcysteine (NAC) 600 mg film-coated tablet (single dose) followed by NAC 600 mg uncoated tablet (single dose) Receives: Drug: N-acetylcysteine

What is being measured

The primary outcome is the main question the study is designed to answer.

Cmax of NAC After Single Dose Administration of Test and Reference
Cmax is the maximum concentration level of the drug reached in plasma.
Measured: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
AUC0-t of NAC After Single Dose Administration of Test and Reference
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.
Measured: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)

Secondary outcomes (5)

AUC0-∞ of NAC After Single Dose Administration of Test and Reference
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.
Measured: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
Tmax of NAC After Single Dose Administration of Test and Reference
time to achieve the maximum concentration level of the drug in plasma.
Measured: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
t1/2 of NAC After Single Dose Administration of Test and Reference
Half-life (t1/2) is the time to halve the plasma concentration level of the drug.
Measured: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
Lambda Zeta of NAC After Single Dose Administration of Test and Reference
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.
Measured: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
Frel of NAC After Single Dose Administration of Test and Reference
Frel is the relative bioavailability, calculated as ratio AUC0-t (test)/ AUC0-t (reference)
Measured: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2014Sep 2014

First posted15 Oct 2014 (estimated)
Study startSep 2014
Primary completionSep 2014
Study completionSep 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for no ConditionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02265224
Sponsor's protocol ID: Z7169J02
Other IDs: CRO-PK-14-286
Status last verified: Oct 2021
First submitted: 3 Oct 2014
Last updated: 5 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparative Bioavailability Study of N-acetyl-cysteine (NAC) 600 mg Uncoated Tablets vs. NAC 600 mg Film-coated Tablets in Healthy Male and Female Volunteers
ClinicalTrials.gov ID: NCT02265224
Acronym / sponsor ID: Z7169J02
Conditions: no Condition
Keywords: healthy volunteers
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Zambon SpAIndustry (pharma, biotech, devices)
Study start: Sep 2014
Primary completion: Sep 2014 (actual)
Study completion: Sep 2014 (actual)
First posted: 15 Oct 2014 (estimated)
Results: Posted 5 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study primary Objective:

To evaluate the bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of N-acetyl-cysteine 600 mg uncoated tablets vs. N-acetyl-cysteine 600 mg film-coated tablets (NAC) in healthy male and female volunteers.

Study secondary objectives:

To describe the pharmacokinetic (PK) profile of NAC in plasma after single dose administration of NAC 600 mg uncoated tablets vs. NAC 600 mg film-coated tablets;
to collect safety and tolerability data after single dose administration of NAC 600 mg uncoated tablets vs. NAC 600 mg film-coated tablets.

Detailed description

This is single centre, single dose, open, randomised, cross-over, two-stage bioequivalence study to compare two different oral formulations of NAC.

The study has been conducted in healthy volunteers of both genders, in one single dose of both formulations.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Test - Reference	Experimental	Drug: N-acetylcysteineN-acetylcysteine (NAC) 600 mg uncoated tablet (single dose) followed by NAC 600 mg film-coated tablet (single dose)
Reference - Test	Active comparator	Drug: N-acetylcysteineN-acetylcysteine (NAC) 600 mg film-coated tablet (single dose) followed by NAC 600 mg uncoated tablet (single dose)

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

Informed consent: signed written informed consent before inclusion in the study
Sex and age: males and females,18-55 years old, inclusive
Body Mass Index (BMI): 18.5-30 kg/m2, inclusive
Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min of rest in the sitting position
Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study

Key exclusion criteria (13 listed)

Electrocardiogram (ECG 12-leads, supine position): clinically significant abnormalities
Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study
Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
N-acetylcysteineAlso: Fluimucil uncoated tabletsThe 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.	Drug	Reference - Test, Test - Reference

Primary outcome

Cmax of NAC After Single Dose Administration of Test and Reference
Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
Cmax is the maximum concentration level of the drug reached in plasma.
AUC0-t of NAC After Single Dose Administration of Test and Reference
Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
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.

5 secondary outcomes

AUC0-∞ of NAC After Single Dose Administration of Test and Reference
Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
Tmax of NAC After Single Dose Administration of Test and Reference
Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
t1/2 of NAC After Single Dose Administration of Test and Reference
Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
Lambda Zeta of NAC After Single Dose Administration of Test and Reference
Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)
Frel of NAC After Single Dose Administration of Test and Reference
Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)

Results and safety

Results posted to the registry on 5 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Enrolled Subjects Set	48	48

Primary outcome: Cmax of NAC After Single Dose Administration of Test and Reference

Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose). Mean (Standard Deviation). Unit: ng/mL

Measure	Test n = 48	Reference n = 48
Value	2804.38 (899.47)	3215.63 (1382.02)

Test vs Reference: Geometric means ratio: 89.81 (94.12% CI 82.82 to 97.40), p = 0.0136, ANOVA

Population analysed: 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.

Primary outcome: AUC0-t of NAC After Single Dose Administration of Test and Reference

Time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose). Mean (Standard Deviation). Unit: ng/mL*h

Measure	Test n = 48	Reference n = 48
Value	10637.87 (3100.94)	11773.11 (3775.43)

Test vs Reference: Geometric means ratio: 90.79 (94.12% CI 85.25 to 96.69), p = 0.0047, ANOVA

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the beginning of screening days ( day -21 ) up to Final Visit (Day 2).. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Test - Reference	0 of 48 (0%)	4 of 48 (8.3%)	0 of 48
Reference - Test	0 of 48 (0%)	2 of 48 (4.2%)	0 of 48

Limitations and caveats (from the sponsor): Limitations and Caveats not specified

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Milko Radicioni, MD principal investigator

Cross Research SA

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing N-acetylcysteine in people with no Condition, run by Zambon SpA.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cmax of NAC After Single Dose Administration of Test and Reference (time frame: 0-24h (5,15, 30, 45, 60, 75, 90 min and 2, 3, 4, 6, 8, 12, 16 and 24 h postdose)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02265224.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.