BioequivalencyPhase 1NCT01229280
Single Dose Bioequivalence Study of Darifenacin Tablets 7.5 mg in Fed 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 proposed study was designed as a randomized two-sequence, two period crossover trial to assess the bioequivalence, pharmacokinetic profiling and safety of a brand generic formulation of darifenacin [Darisec(R) 7.5 mg] vs. the innovator [Enablex(R)7.5 mg]in healthy volunteers in postprandial state. 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
- Dec 2010to Feb 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 glaucoma, 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 drug 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 which 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 results.
- 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 (vitamins, herbal supplements, dietary supplements)within 2 weeks prior to dosing. Paracetamol and ibuprofen are acceptable.
- Participation in any clinical investigation within 12 weeks prior to dosing.
- Donation or loss of 400 ml or more of blood within 8 weeks 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 (CCPR) Bdbeq S.A. Hospital Italiano.
Montevideo, Montevideo Department, 11600
Francisco E. Estevez-Carrizo, M.D., +59824876288, francisco.estevez@bdbeq.com.uy
Mónica Cedrés, Pharm. B., +59824876288, mcderes@bdbeq.com.uy
About this study
Official title: Comparative Bioavailability of Darifenacin Extended Release Oral Formulation [Darisec(R)7.5 mg vs. Enablex(R)7.5 mg]: Single-dose, Postprandial State, Randomized, Two-sequence, Two-period, Crossover Study in Healthy Volunteers.
The proposed study was designed as a randomized two-sequence, two period crossover trial to assess the bioequivalence, pharmacokinetic profiling and safety of a brand generic formulation of darifenacin [Darisec(R) 7.5 mg] vs. the innovator [Enablex(R)7.5 mg]in healthy volunteers in postprandial state.
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. A bioequivalence study will be performed to validate pharmaceutical development before introducing the product in the market.
The purpose in this study is to evaluate the relative bioavailability, pharmacokinetic profiling and safety of a brand generic formulation of darifenacin [Darisec(R) 7.5 mg] vs. the innovator [Enablex(R) 7.5 mg]in 24 healthy uruguayan volunteers after a high fat breakfast of 1000 calories (50% fat, 35% carbohydrates, and 15% proteins)to establish their average bioequivalence.
The bioequivalence will be evaluated using:
- The Area Under the Curve (AUC),
- The peak plasma concentration (Cmax).
The pharmacokinetic characteristics of the drug formulations will be described calculating:
- The time to peak concentration (Tmax)
- The elimination constant (Ke)
- The elimination half-life (t1/2e)
- The systemic clearance (Cls)
Safety will be evaluated recording:
- Reported adverse events
- Vital signs (blood pressure, heart rate, body temperature)
- 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 requirements:
- Mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
- Mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25
Pharmacokinetic profiling will be evaluated by describing the pharmacokinetic characteristics of both drug in adequate two-way tables.
Safety will be evaluated comparing incidence of adverse events/adverse effects for both products.
- Conditions
- Bioequivalency
- Being tested
- Darifenacin
- Keywords
- Bioequivalence, Darifenacin, 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 antagonist, Cholinergic antagonist, Cholinergic agent, Darisec
Single dose 7.5 mg tablets of darifenacin
DarifenacinDrug
Also called Muscarinec antagonist, Cholinergic antagonist, Cholinergic agent, Enablex
Single dose 7.5 mg tablets of Darifenacin
| Study group | Role | What they receive |
|---|---|---|
| Darisec(R) 7.5 mg | Experimental | Not described Receives: Drug: Darifenacin |
| Enablex(R) 7.5 mg | Active comparator | 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 the plasma concentration 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 abosorption will be measured using peak concentration of darifenacin (Cmax)taken from the concentration vs. time curve.
Measured: 72
Secondary outcomes (4)
Time to peak concentration (tmax)
Tmax is the time elapsed from ingestion of darifenacin tablets to plasma peak concentration (Cmax)
Measured: 72
Elimination rate constant (Ke)
The elimination rate constant is the fractional rate of drug disappearance form the peripheral compartement, measured in the log-linear elimination phase.
Measured: 72 hours
Elimination Half-life (t1/2e)
t1/2e is the time in which the concentration in the log-linear elimination phase drops by half.
Measured: 72 hours
Systemic clearance (Cls)
Cls is the amount of plasma volume units that are totally cleared of the drug in the unit of time.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2010 (estimated)
- Study startDec 2010
- Primary completionJan 2011 (estimated)
- Study completionFeb 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- NCT01229280
- Sponsor's protocol ID
- BDBEQ_DFNLP/ELEA_010
- Status last verified
- Oct 2010
- First submitted
- 26 Oct 2010
- Last updated
- 27 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 16584282Croom KF, Keating GM. Darifenacin: in the treatment of overactive bladder. Drugs Aging. 2004;21(13):885-92; discussion 893-4. doi: 10.2165/00002512-200421130-00005.
PubMed 15493952Staskin DR. Overactive bladder in the elderly: a guide to pharmacological management. Drugs Aging. 2005;22(12):1013-28. doi: 10.2165/00002512-200522120-00003.
PubMed 16363885Kerbusch T, Wahlby U, Milligan PA, Karlsson MO. Population pharmacokinetic modelling of darifenacin and its hydroxylated metabolite using pooled data, incorporating saturable first-pass metabolism, CYP2D6 genotype and formulation-dependent bioavailability. Br J Clin Pharmacol. 2003 Dec;56(6):639-52. doi: 10.1046/j.1365-2125.2003.01967.x.
PubMed 14616424Dmochowski RR, Appell RA. Advancements in pharmacologic management of the overactive bladder. Urology. 2000 Dec 4;56(6 Suppl 1):41-9. doi: 10.1016/s0090-4295(00)01020-7.
PubMed 11114562
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Bioavailability of Darifenacin Extended Release Oral Formulation [Darisec(R)7.5 mg vs. Enablex(R)7.5 mg]: Single-dose, Postprandial State, Randomized, Two-sequence, Two-period, Crossover Study in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT01229280
- Acronym / sponsor ID
- BDBEQ_DFNLP/ELEA_010
- Conditions
- Bioequivalency
- Keywords
- Bioequivalence, Darifenacin, 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
- Dec 2010
- Primary completion
- Jan 2011 (estimated)
- Study completion
- Feb 2011 (estimated)
- First posted
- 27 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 proposed study was designed as a randomized two-sequence, two period crossover trial to assess the bioequivalence, pharmacokinetic profiling and safety of a brand generic formulation of darifenacin [Darisec(R) 7.5 mg] vs. the innovator [Enablex(R)7.5 mg]in healthy volunteers in postprandial state.
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. A bioequivalence study will be performed to validate pharmaceutical development before introducing the product in the market.
The purpose in this study is to evaluate the relative bioavailability, pharmacokinetic profiling and safety of a brand generic formulation of darifenacin [Darisec(R) 7.5 mg] vs. the innovator [Enablex(R) 7.5 mg]in 24 healthy uruguayan volunteers after a high fat breakfast of 1000 calories (50% fat, 35% carbohydrates, and 15% proteins)to establish their average bioequivalence.
The bioequivalence will be evaluated using:
- The Area Under the Curve (AUC),
- The peak plasma concentration (Cmax).
The pharmacokinetic characteristics of the drug formulations will be described calculating:
- The time to peak concentration (Tmax)
- The elimination constant (Ke)
- The elimination half-life (t1/2e)
- The systemic clearance (Cls)
Safety will be evaluated recording:
- Reported adverse events
- Vital signs (blood pressure, heart rate, body temperature)
- 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 requirements:
- Mean AUCt/AUCr and 90% confidence interval within 0.80-1.25
- Mean Cmaxt/Cmaxr and 90% confidence interval within 0.80-1.25
Pharmacokinetic profiling will be evaluated by describing the pharmacokinetic characteristics of both drug in adequate two-way tables.
Safety will be evaluated comparing incidence 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 |
|---|---|---|
| Darisec(R) 7.5 mg | Experimental | Drug: Darifenacin |
| Enablex(R) 7.5 mg | Active comparator | 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 glaucoma, 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 antagonist, Cholinergic antagonist, Cholinergic agent, DarisecSingle dose 7.5 mg tablets of darifenacin | Drug | Darisec(R) 7.5 mg |
| DarifenacinAlso: Muscarinec antagonist, Cholinergic antagonist, Cholinergic agent, EnablexSingle dose 7.5 mg tablets of Darifenacin | Drug | Enablex(R) 7.5 mg |
Primary outcome
Extent of absorption
Time frame: 72 hours
Extent of absorption will be measured using the area under the plasma concentration 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 abosorption will be measured using peak concentration of darifenacin (Cmax)taken from the concentration vs. time curve.
4 secondary outcomes
Time to peak concentration (tmax)
Time frame: 72
Elimination rate constant (Ke)
Time frame: 72 hours
Elimination Half-life (t1/2e)
Time frame: 72 hours
Systemic clearance (Cls)
Time frame: 72 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2010.
- Background: PubMed 16584282Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50. doi: 10.2165/00003088-200645040-00001.
- Background: PubMed 15493952Croom KF, Keating GM. Darifenacin: in the treatment of overactive bladder. Drugs Aging. 2004;21(13):885-92; discussion 893-4. doi: 10.2165/00002512-200421130-00005.
- Background: PubMed 16363885Staskin DR. Overactive bladder in the elderly: a guide to pharmacological management. Drugs Aging. 2005;22(12):1013-28. doi: 10.2165/00002512-200522120-00003.
- Background: PubMed 14616424Kerbusch T, Wahlby U, Milligan PA, Karlsson MO. Population pharmacokinetic modelling of darifenacin and its hydroxylated metabolite using pooled data, incorporating saturable first-pass metabolism, CYP2D6 genotype and formulation-dependent bioavailability. Br J Clin Pharmacol. 2003 Dec;56(6):639-52. doi: 10.1046/j.1365-2125.2003.01967.x.
- Background: PubMed 11114562Dmochowski RR, Appell RA. Advancements in pharmacologic management of the overactive bladder. Urology. 2000 Dec 4;56(6 Suppl 1):41-9. doi: 10.1016/s0090-4295(00)01020-7.
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 27 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 NCT01229280, which also lists 5 linked publications.
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 27 Oct 2010.