Erectile DysfunctionPhase 1NCT00770042
To Evaluate The Effect Of Ketoconazole, Ritonavir and Erythromycin on the Safety and Pharmacokinetics of Avanafil
A Phase 1 study testing Ritonavir, Ketoconazole and Erythomycin in people with Erectile Dysfunction, run by VIVUS LLC at 1 site in United States.
Trial summary
This study is being conducted to examine the effect of three CYP3A4 inhibitors (ketoconazole, erythromycin and ritonavir) on the single dose pharmacokinetics of avanafil. Ketoconazole and ritonavir are potent inhibitors of CYP3A4 and erythromycin is a moderate CYP3A4 inhibitor. Read more about this study
- Who is it for?
- Ages 21 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Erectile Dysfunction
- What is being tested?
- Ritonavir, Ketoconazole and Erythomycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Dec 2008
- 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 21 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males, 21 to 45 years of age (inclusive).
- A body weight of at least 50 kg and a body mass index (BMI) between 21 and 28 kg/m2, inclusive
- Medically healthy, with clinically insignificant screening results [e.g., laboratory profiles, medical histories, ECGs, physical exam, etc., in the opinion of the investigator.
- Subjects are able to communicate with the investigator, and to understand and comply with all requirements of study participation.
- Voluntarily consent to participate in the study
- The subject must agree not to donate his sperm during and within 3-months of the completion of the study.
- All sexually active male subjects and their female partners of childbearing potential must agree to use adequate contraception methods, for the specified time.
Who cannot join
- A history or presence of significant cardiovascular, neurological, hematological, psychiatric, hepatic, gastrointestinal, pulmonary, endocrine, immunologic or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs or place the subjects at increased risk as determined by the investigator.
- Any clinically significant laboratory abnormalities as judged by the investigator.
- Systolic blood pressure < 90 or >140 mmHg; diastolic blood pressure < 50 or > 90 mmHg at screening or at check-in on day 1 in treatment period 1.
- Positive urine drug test and/or positive breath alcohol test.
- Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) at screening.
- Any history or presence of alcoholism or drug or substance abuse.
Show all 14Show fewer
- Allergy to or previous adverse events with PDE5 inhibitors, ketoconazole, ritonavir and/or erythromycin or their constituents.
- Use of any prescription or over-the-counter (OTC) medication, including herbal products.
- Use of any drugs known to have clinical significance in inhibiting or inducing liver enzymes involved in drug metabolism
- Blood donation or significant blood loss.
- Any use of tobacco or nicotine products within 6 months.
- Any history of celiac diseases, food allergies, and those on vegetarian or other diets incompatible with study objectives.
- Any subject who received an investigational drug within 30 days .
- Clinical judgment by the investigator that the subject should not participate in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Single-Centre, Open-Label, Randomized, One-sequence Crossover, Three-Group Study to Evaluate the Effect of Ketoconazole, Ritonavir and Erythromicin on the Safety and Pharmacokinetics of Avanafil (TA-1790) in Healthy Male Subjects
This study is being conducted to examine the effect of three CYP3A4 inhibitors (ketoconazole, erythromycin and ritonavir) on the single dose pharmacokinetics of avanafil. Ketoconazole and ritonavir are potent inhibitors of CYP3A4 and erythromycin is a moderate CYP3A4 inhibitor. Any interaction that is observed would be predictive of other inhibitors of CYP3A4.
Read the detailed description
Rationale:
Erectile dysfunction (ED) is the persistent or recurrent inability to attain and maintain penile erection sufficient to permit satisfactory sexual performance. The current first-line treatment for ED consists of oral therapy with phosphodiesterase type 5 (PDE5) inhibitors. These drugs prevents the hydrolysis of cyclic guanosine monophosphate (cGMP), resulting in increased levels of cGMP and decreased Ca+2 concentrations in the smooth muscle cells of the erectile tissues, smooth muscle relaxation and increased blood flow into the penis. The drugs are extensively metabolized in human liver microsomes, and involve the cytochrome P450, CYP2C subfamily and CYP3A4. This enzyme system is readily inhibited by many drugs. When enzymes that metabolize PDE5 inhibitors are inhibited, there may be increased plasma concentrations of the drugs and possible increases in or prolongation of therapeutic and/or adverse effects.
Avanafil is a potent and highly specific PDE5 inhibitor that is rapidly absorbed from the gastrointestinal tract and that has a relatively short half-life (0.55-1.2 hours). The formation of the main metabolites of avanafil is catalyzed by CYP3A4. It is possible that the pharmacokinetics of avanafil may be modified by drugs that block the cytochrome P450 enzyme pathways, resulting in significant changes in its pharmacokinetic (PK), efficacy and adverse event profiles. This study is being conducted to examine the effect of three CYP3A4 inhibitors (ketoconazole, erythromycin and ritonavir) on the single dose pharmacokinetics of avanafil.
Ketoconazole and ritonavir are potent inhibitors of CYP3A4 and erythromycin is a moderate CYP3A4 inhibitor. Any interaction that is observed would be predictive of other inhibitors of CYP3A4
- Conditions
- Erectile Dysfunction
- Being tested
- Ritonavir, Ketoconazole, Erythomycin, Avanafil
- Medical subject headings
- Erectile Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RitonavirDrug
Ritonavir 300 mg bid for 1 day (Day 2), 400 mg bid for 1 day (Day 3), 600 mg bid for 5 days (Day 4-8)
KetoconazoleDrug
Ketoconazole 400 mg qd for 5 days (Days 2-6)
ErythomycinDrug
Erythromycin 500 mg every 12 hours for 5 days (Days 2-6)
AvanafilDrug
Avanafil 50 mg on Days 1 and 8
AvanafilDrug
Avanafil 50 mg on Days 1 and 6
AvanafilDrug
Avanafil 200mg Days 1 and 6
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Ketoconazole 400 mg qd for 5 days (Days 2-6) plus a single dose of 50 mg avanafil on Days 1 and 6 Receives: Drug: Ketoconazole; Drug: Avanafil |
| Group 2 | Experimental | Erythromycin 500mg every 12 hours for 5 days (Days 2-6) plus a single dose of 200 mg Avanafil on Days 1 and 6. Receives: Drug: Erythomycin; Drug: Avanafil |
| Group 3 | Experimental | Ritonavir 300 mg bid for 1 day (Day 2), 400 mg bid for 1 day (Day 3), 600 mg bid for 5 days (Day 4-8) plus a single dose of 50 mg avanafil on Days 1 and 8 Receives: Drug: Ritonavir; Drug: Avanafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety of avanafil when administered with Ketoconazole, ritonavir, or erythromycin and to assess the effect of co-administration of these drugs on the pharmacokinetics of avanafil
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionNov 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Erectile DysfunctionStudies 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
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- VIVUS LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Shiyin Yee, PhD, Study director, VIVUS LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00770042
- Sponsor's protocol ID
- TA-011
- Status last verified
- Nov 2009
- First submitted
- 6 Oct 2008
- Last updated
- 2 Dec 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single-Centre, Open-Label, Randomized, One-sequence Crossover, Three-Group Study to Evaluate the Effect of Ketoconazole, Ritonavir and Erythromicin on the Safety and Pharmacokinetics of Avanafil (TA-1790) in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT00770042
- Acronym / sponsor ID
- TA-011
- Conditions
- Erectile Dysfunction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- VIVUS LLCIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Nov 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 9 Oct 2008 (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.
This study is being conducted to examine the effect of three CYP3A4 inhibitors (ketoconazole, erythromycin and ritonavir) on the single dose pharmacokinetics of avanafil. Ketoconazole and ritonavir are potent inhibitors of CYP3A4 and erythromycin is a moderate CYP3A4 inhibitor. Any interaction that is observed would be predictive of other inhibitors of CYP3A4.
Detailed description
Rationale:
Erectile dysfunction (ED) is the persistent or recurrent inability to attain and maintain penile erection sufficient to permit satisfactory sexual performance. The current first-line treatment for ED consists of oral therapy with phosphodiesterase type 5 (PDE5) inhibitors. These drugs prevents the hydrolysis of cyclic guanosine monophosphate (cGMP), resulting in increased levels of cGMP and decreased Ca+2 concentrations in the smooth muscle cells of the erectile tissues, smooth muscle relaxation and increased blood flow into the penis. The drugs are extensively metabolized in human liver microsomes, and involve the cytochrome P450, CYP2C subfamily and CYP3A4. This enzyme system is readily inhibited by many drugs. When enzymes that metabolize PDE5 inhibitors are inhibited, there may be increased plasma concentrations of the drugs and possible increases in or prolongation of therapeutic and/or adverse effects.
Avanafil is a potent and highly specific PDE5 inhibitor that is rapidly absorbed from the gastrointestinal tract and that has a relatively short half-life (0.55-1.2 hours). The formation of the main metabolites of avanafil is catalyzed by CYP3A4. It is possible that the pharmacokinetics of avanafil may be modified by drugs that block the cytochrome P450 enzyme pathways, resulting in significant changes in its pharmacokinetic (PK), efficacy and adverse event profiles. This study is being conducted to examine the effect of three CYP3A4 inhibitors (ketoconazole, erythromycin and ritonavir) on the single dose pharmacokinetics of avanafil.
Ketoconazole and ritonavir are potent inhibitors of CYP3A4 and erythromycin is a moderate CYP3A4 inhibitor. Any interaction that is observed would be predictive of other inhibitors of CYP3A4
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Ketoconazole, Drug: AvanafilKetoconazole 400 mg qd for 5 days (Days 2-6) plus a single dose of 50 mg avanafil on Days 1 and 6 |
| Group 2 | Experimental | Drug: Erythomycin, Drug: AvanafilErythromycin 500mg every 12 hours for 5 days (Days 2-6) plus a single dose of 200 mg Avanafil on Days 1 and 6. |
| Group 3 | Experimental | Drug: Ritonavir, Drug: AvanafilRitonavir 300 mg bid for 1 day (Day 2), 400 mg bid for 1 day (Day 3), 600 mg bid for 5 days (Day 4-8) plus a single dose of 50 mg avanafil on Days 1 and 8 |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Males, 21 to 45 years of age (inclusive).
- A body weight of at least 50 kg and a body mass index (BMI) between 21 and 28 kg/m2, inclusive
- Medically healthy, with clinically insignificant screening results [e.g., laboratory profiles, medical histories, ECGs, physical exam, etc., in the opinion of the investigator.
- Subjects are able to communicate with the investigator, and to understand and comply with all requirements of study participation.
- Voluntarily consent to participate in the study
Key exclusion criteria (14 listed)
- A history or presence of significant cardiovascular, neurological, hematological, psychiatric, hepatic, gastrointestinal, pulmonary, endocrine, immunologic or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs or place the subjects at increased risk as determined by the investigator.
- Any clinically significant laboratory abnormalities as judged by the investigator.
- Systolic blood pressure < 90 or >140 mmHg; diastolic blood pressure < 50 or > 90 mmHg at screening or at check-in on day 1 in treatment period 1.
- Positive urine drug test and/or positive breath alcohol test.
- Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) at screening.
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 |
|---|---|---|
| RitonavirRitonavir 300 mg bid for 1 day (Day 2), 400 mg bid for 1 day (Day 3), 600 mg bid for 5 days (Day 4-8) | Drug | Group 3 |
| KetoconazoleKetoconazole 400 mg qd for 5 days (Days 2-6) | Drug | Group 1 |
| ErythomycinErythromycin 500 mg every 12 hours for 5 days (Days 2-6) | Drug | Group 2 |
| AvanafilAvanafil 50 mg on Days 1 and 8 | Drug | Group 3 |
| AvanafilAvanafil 50 mg on Days 1 and 6 | Drug | Group 1 |
| AvanafilAvanafil 200mg Days 1 and 6 | Drug | Group 2 |
Primary outcome
Evaluate the safety of avanafil when administered with Ketoconazole, ritonavir, or erythromycin and to assess the effect of co-administration of these drugs on the pharmacokinetics of avanafil
Time frame: 9 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2009.
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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.
Shiyin Yee, PhD study director
VIVUS LLC
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 Ritonavir, Ketoconazole and Erythomycin in people with Erectile Dysfunction, run by VIVUS LLC at 1 site in United States.
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 7 inclusion and 14 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 2 Dec 2009. 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 United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluate the safety of avanafil when administered with Ketoconazole, ritonavir, or erythromycin and to assess the effect of co-administration of these drugs on the pharmacokinetics of avanafil (time frame: 9 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2009.