BioequivalencyPhase 1NCT01227811
Single Dose Two-periods Crossover Bioequivalence Study of Darifenacin Tablets in Healthy Volunteers.
A Phase 1 study testing Darifenacin in people with Bioequivalency, run by Center for Clinical Pharmacology Research Bdbeq S.A. at 1 site in Uruguay.
Trial summary
The present study was designed to assess the bioequivalence and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R)]vs. the innovator [Enablex(R)]in healthy volunteers after a high fat breakfast. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Bioequivalency
- What is being tested?
- Darifenacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUruguay
- Study dates
- Nov 2010to Mar 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female subjects 18 to 50 years of age (inclusive)
- In good health, as determined by lack of clinically significant abnormalities at screening as judged by the physician.
- Female subjects are required to use a medically accepted method of hormonal contraception or abstinence throughout the entire study period and for one week after the study is completed.
- Body mass index within the range of 18.5 and 29.9 kg/m2 and weight at least 45 kg.
Who cannot join
- Known hypersensitivity or severe adverse event to darifenacin or similar drugs.
- Urinary retention, narrow-angle glucoma, myasthenia gravis, severe hepatic impairment, severe ulcerative colitis, toxic megacolon.
- Symptomatic hiatus hernia, erosive or symptomatic gastroesophageal reflux disease/heartburn (>2 days in a week), severe constipation, gastrointestinal obstructive disorder, and gastric retention.
- Clinically significant cardiac abnormalities, fainting, low blood pressure upon standing, irregular heartbeats.
- Acute or chronic bronchospastic disease (including asthma and Chronic Obstructive Pulmonary Disease).
- Clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis).
Show all 17Show fewer
- Smokers of more than 5 cigarettes a week.
- Regular use of any drugs known to induce or inhibit hepatic drug metabolism (particularly those that affect CYP2D6) within 30 days prior to each study drug administration.
- Any surgical or medical condition wich might significantly alter the absorption, distribution, metabolism or excretion of drugs which may jeopardize participation in the study.
- Immunodeficiency diseases, including a positive HIV (Elisa or Western blot) test result.
- Positive hepatitis B Surface antigen (HBsAg) or Hepatitis C test result.
- Drug or alcohol abuse within the 6 months prior to dosing.
- Use of prescription drugs within 1 month prior to dosing, or over-the-counter medication (vitamine, herbal supplements, dietary supplements) within 2 weeks prior to dosing. Paracetamol and ibuprofen are acceptable.
- Participation in any clinical investigation within 4 weeks prior to dosing.
- Donation or loss of 400 ml or more of blood within 2 months prior to dosing.
- significant illness within 2 weeks prior to dosing.
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
1 site in 1 country.
Uruguay1 site
Center for Clinical Pharmacology Research Bdbeq S.A.; Hospital Italiano de Montevideo..
Montevideo, Montevideo Department, 11600
Susana Parrillo, MD, +59824876288 ext. 201, sparrillo@bdbeq.com.uy
Mónica Cedrés, Pharm. B., +59824876288 ext. 202, mcedres@bdbeq.com.uy
About this study
Official title: Single Dose, Two-period, Crossover, Fed Bioequivalence Study of Darifenacin Extended Release Oral Formulation (Darisec(R) 15 mg) vs. Enablex(R) 15 mg in Healthy Volunteers.
The present study was designed to assess the bioequivalence and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R)]vs. the innovator [Enablex(R)]in healthy volunteers after a high fat breakfast.
The bioequivalence will be evaluated using:
- the Area Under the Curve (AUC) and,
- the peak plasma concentration (Cmax).
Safety will be evaluated recording:
- vital signs
- adverse events,
- laboratory analysis.
- EKG and chest XRays.
Bioequivalence will be claimed if the drugs comply with local regulatory requirement, eg.:
- mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
- mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25.
Read the detailed description
Darifenacin is a muscarinic receptor antagonist drug used to treat overactive bladder. There is a new formulation of darifenacin extended release developed by an argentinian pharmaceutical company and, according to regional regulations, a bioequivalence study should be performed to put it in the market.
The purpose of this study is to evaluate the relative bioavailability and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R) 15 mg] vs. the innovator [Enablex(R) 15 mg] in 24 healthy uruguayan volunteers after a high fat breakfast of 1000 calories (50% fat, 35% carbohydrates (sugar, flour, etc.) and 15\& proteins) to establish their average bioequivalence.
The bioequivalence will be evaluated using outcome measures that will be described later.
The pharmacokinetic characteristics of the drugs will be described calculating:
- the time to Cmax (Tmax)
- the elimination constant (Ke),
- the elimination half-life (t1/2e)and,
- the systemic clearance (Cls.
Safety will be evaluated recording:
- vital signs (blood pressure, heart rate, body temperature)
- adverse events,
- laboratory analysis (hemogram, hepatic enzymes, creatinine, sugar in blood,etc.).
- EKG and chest XRays.
Bioequivalence will be claimed if the drugs comply with local and FDA regulatory requirement, eg.:
- mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
- mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25.
Safety will be evaluated comparing incidences of adverse events/adverse effects for both products.
- Conditions
- Bioequivalency
- Being tested
- Darifenacin
- Keywords
- Darifenacin, Bioequivalence, Healthy volunteers, Postprandial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DarifenacinDrug
Also called Muscarinic Antagonists, Cholinergic Antagonists, Cholinergic Agents, Enablex
Single oral dose Darisec(R) 15.0 mg
DarifenacinDrug
Single oral dose Enablex(R) 15 mg
| Study group | Role | What they receive |
|---|---|---|
| Enablex(R) 15 mg , single dose | Active comparator | Not described Receives: Drug: Darifenacin |
| Darifenacin 15 mg tablets, single dose | Experimental | Not described Receives: Drug: Darifenacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extent of Absorption.
Extent of absorption will be measured using the area under plasma concentrations of darifenacin vs. time from time 0 to the last sample point (AUC0-t) and from time 0 to infinity (AUC0-inf).
Measured: 72 hours
Rate of Absorption
Rate of abosrption will be measured using the peak concentration of darifenacin (Cmax).
Measured: 72
Secondary outcomes (3)
Time to peak concentration (tmax)
Is the time elapsed from ingestion of darifenacin tablets to plasma peak concentration.
Measured: 72 hours
Absorption Rate Constant(Ka)
The absorption rate constant is the fractional rate of drug disappearance from the intestinal tract, measured in the log-linear phase of drug absorption.
Measured: 72 hours
Elimination Rate Constant (Ke)
The elimiminaiton rate constant is the fractional rate of drug dissapearance from the peripheral compartment, measured in the log-linear phase of elimination.
Measured: 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2010 (estimated)
- Study startNov 2010
- Primary completionDec 2010 (estimated)
- Study completionMar 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BioequivalencyStudies 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Center for Clinical Pharmacology Research Bdbeq S.A.
- Sponsor type
- University, hospital or other
- Collaborators
- Laboratorio Elea Phoenix S.A.
- Investigators
- Francisco E. Estevez-Carrizo, MD, Study director, Univerisity of Montevideo. Biomedical Science Center.Prudencio de Pena 2440, 11600 Montevideo. UruguaySusana Parrillo, M.D., Principal investigator, Center for Clinical Pharmacology Research Bdbeq S.A., Br. Artigas 1632. c.p. 11600 Montevideo. Uruguay.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01227811
- Sponsor's protocol ID
- BDBEQ_DFNLP/ELEA_011
- Status last verified
- Oct 2010
- First submitted
- 18 Oct 2010
- Last updated
- 25 Oct 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50. doi: 10.2165/00003088-200645040-00001.
PubMed 16584282
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Dose, Two-period, Crossover, Fed Bioequivalence Study of Darifenacin Extended Release Oral Formulation (Darisec(R) 15 mg) vs. Enablex(R) 15 mg in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT01227811
- Acronym / sponsor ID
- BDBEQ_DFNLP/ELEA_011
- Conditions
- Bioequivalency
- Keywords
- Darifenacin, Bioequivalence, Healthy volunteers, Postprandial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Center for Clinical Pharmacology Research Bdbeq S.A.University, hospital or other
- Collaborators
- Laboratorio Elea Phoenix S.A.
- Study start
- Nov 2010
- Primary completion
- Dec 2010 (estimated)
- Study completion
- Mar 2011 (estimated)
- First posted
- 25 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study was designed to assess the bioequivalence and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R)]vs. the innovator [Enablex(R)]in healthy volunteers after a high fat breakfast.
The bioequivalence will be evaluated using:
- the Area Under the Curve (AUC) and,
- the peak plasma concentration (Cmax).
Safety will be evaluated recording:
- vital signs
- adverse events,
- laboratory analysis.
- EKG and chest XRays.
Bioequivalence will be claimed if the drugs comply with local regulatory requirement, eg.:
- mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
- mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25.
Detailed description
Darifenacin is a muscarinic receptor antagonist drug used to treat overactive bladder. There is a new formulation of darifenacin extended release developed by an argentinian pharmaceutical company and, according to regional regulations, a bioequivalence study should be performed to put it in the market.
The purpose of this study is to evaluate the relative bioavailability and pharmacokinetic profiling of a brand generic formulation of darifenacin [Darisec(R) 15 mg] vs. the innovator [Enablex(R) 15 mg] in 24 healthy uruguayan volunteers after a high fat breakfast of 1000 calories (50% fat, 35% carbohydrates (sugar, flour, etc.) and 15\& proteins) to establish their average bioequivalence.
The bioequivalence will be evaluated using outcome measures that will be described later.
The pharmacokinetic characteristics of the drugs will be described calculating:
- the time to Cmax (Tmax)
- the elimination constant (Ke),
- the elimination half-life (t1/2e)and,
- the systemic clearance (Cls.
Safety will be evaluated recording:
- vital signs (blood pressure, heart rate, body temperature)
- adverse events,
- laboratory analysis (hemogram, hepatic enzymes, creatinine, sugar in blood,etc.).
- EKG and chest XRays.
Bioequivalence will be claimed if the drugs comply with local and FDA regulatory requirement, eg.:
- mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
- mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25.
Safety will be evaluated comparing incidences of adverse events/adverse effects for both products.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enablex(R) 15 mg , single dose | Active comparator | Drug: Darifenacin |
| Darifenacin 15 mg tablets, single dose | Experimental | Drug: Darifenacin |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy male or female subjects 18 to 50 years of age (inclusive)
- In good health, as determined by lack of clinically significant abnormalities at screening as judged by the physician.
- Female subjects are required to use a medically accepted method of hormonal contraception or abstinence throughout the entire study period and for one week after the study is completed.
- Body mass index within the range of 18.5 and 29.9 kg/m2 and weight at least 45 kg.
Key exclusion criteria (17 listed)
- Known hypersensitivity or severe adverse event to darifenacin or similar drugs.
- Urinary retention, narrow-angle glucoma, myasthenia gravis, severe hepatic impairment, severe ulcerative colitis, toxic megacolon.
- Symptomatic hiatus hernia, erosive or symptomatic gastroesophageal reflux disease/heartburn (>2 days in a week), severe constipation, gastrointestinal obstructive disorder, and gastric retention.
- Clinically significant cardiac abnormalities, fainting, low blood pressure upon standing, irregular heartbeats.
- Acute or chronic bronchospastic disease (including asthma and Chronic Obstructive Pulmonary Disease).
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 |
|---|---|---|
| DarifenacinAlso: Muscarinic Antagonists, Cholinergic Antagonists, Cholinergic Agents, EnablexSingle oral dose Darisec(R) 15.0 mg | Drug | Darifenacin 15 mg tablets, single dose |
| DarifenacinSingle oral dose Enablex(R) 15 mg | Drug | Enablex(R) 15 mg , single dose |
Primary outcome
Extent of Absorption.
Time frame: 72 hours
Extent of absorption will be measured using the area under plasma concentrations of darifenacin vs. time from time 0 to the last sample point (AUC0-t) and from time 0 to infinity (AUC0-inf).
Rate of Absorption
Time frame: 72
Rate of abosrption will be measured using the peak concentration of darifenacin (Cmax).
3 secondary outcomes
Time to peak concentration (tmax)
Time frame: 72 hours
Absorption Rate Constant(Ka)
Time frame: 72 hours
Elimination Rate Constant (Ke)
Time frame: 72
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2010.
- Background: PubMed 16584282Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50. doi: 10.2165/00003088-200645040-00001.
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.
Francisco E. Estevez-Carrizo, MD study director
Univerisity of Montevideo. Biomedical Science Center.Prudencio de Pena 2440, 11600 Montevideo. Uruguay
Susana Parrillo, M.D. principal investigator
Center for Clinical Pharmacology Research Bdbeq S.A., Br. Artigas 1632. c.p. 11600 Montevideo. Uruguay.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Darifenacin in people with Bioequivalency, run by Center for Clinical Pharmacology Research Bdbeq S.A. at 1 site in Uruguay.
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 4 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 25 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uruguay. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Federico Santoro, MD (+541143794300, santorof@elea.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extent of Absorption. (time frame: 72 hours). 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 NCT01227811, which also lists 1 linked publication.
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 25 Oct 2010.