HealthyPhase 1NCT01426958

Investigation of Ritonavir Effects on Afatinib Exposure in Healthy Subjects

A Phase 1 study testing afatinib and ritonavir + afatinib in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

Completed

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

Official record

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Trial summary

To study the effect of the P-glycoprotein inhibitor ritonavir on the pharmacokinetics (PK) of afatinib depending on the timepoint of ritonavir administration Read more about this study

Who is it for?: Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: afatinib and ritonavir + afatinib
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 siteGermany
Study dates: Aug 2011to Dec 2011
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
Men only
Healthy volunteers accepted
Adult

Who may be able to join

1. healthy male subjects

Who cannot join

1. any relevant deviation from healthy conditions

Trial locations and contacts

1 site in 1 country.

Germany1 site

1200.151.1 Boehringer Ingelheim Investigational Site
Biberach

Other trials in Germany

About this study

Official title: Relative Bioavailability of a Single Oral Dose of 40 mg Afatinib Given Alone Compared to Concomitant and Timed Administration of Multiple Oral Doses of Ritonavir - an Open-label, Randomised, Three-way Crossover Trial in Healthy Male Volunteers

To study the effect of the P-glycoprotein inhibitor ritonavir on the pharmacokinetics (PK) of afatinib depending on the timepoint of ritonavir administration

Conditions: Healthy
Being tested: afatinib, ritonavir + afatinib

What participants receive

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

afatinibDrug
standard therapeutic dose
ritonavir + afatinibDrug
simultaneous intake of ritonavir and afatinib on second treatment day
ritonavir + afatinibDrug
on the second treatment day the first ritonavir tablet will be taken 6 hours after the afatinib tablet

Study groups in NCT01426958
Study group	Role	What they receive
treatment A	Active comparator	1 tablet afatinib single dose Receives: Drug: afatinib
treatment B	Experimental	2 x 2 tablets ritonavir for 3 days + 1 tablet afatinib on the second treatment day Receives: Drug: ritonavir + afatinib
treatment C	Experimental	2 x 2 tablets ritonavir for 3 days + 1 tablet afatinib on the second treatment day Receives: Drug: ritonavir + afatinib

What is being measured

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

Area Under Curve From 0 to tz (AUC0-tz)
AUC0-tz represents the area under the concentration curve of the analyte in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte.
Measured: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
Maximum Concentration (Cmax)
Cmax represents the maximum concentration of the analyte in plasma.
Measured: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
Area Under Curve From 0 to ∞ Hours (AUC0-∞)
AUC0-∞ represents the area under the concentration curve of the analyte in plasma from 0 extrapolated to infinity.
Measured: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post

Timeline

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

Aug 2011Dec 2011

First posted1 Sep 2011 (estimated)
Study startAug 2011
Primary completionDec 2011

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 HealthyStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
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: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01426958
Sponsor's protocol ID: 1200.151
Other IDs: 2011-001803-11
Status last verified: Oct 2013
First submitted: 30 Aug 2011
Last updated: 9 Jun 2014
Results posted: Yes, on ClinicalTrials.gov

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?

See locations

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All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Relative Bioavailability of a Single Oral Dose of 40 mg Afatinib Given Alone Compared to Concomitant and Timed Administration of Multiple Oral Doses of Ritonavir - an Open-label, Randomised, Three-way Crossover Trial in Healthy Male Volunteers
ClinicalTrials.gov ID: NCT01426958
Acronym / sponsor ID: 1200.151
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Aug 2011
Primary completion: Dec 2011 (actual)
First posted: 1 Sep 2011 (estimated)
Results: Posted 19 Dec 2013

Clinical summary

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

To study the effect of the P-glycoprotein inhibitor ritonavir on the pharmacokinetics (PK) of afatinib depending on the timepoint of ritonavir administration

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
treatment A	Active comparator	Drug: afatinib1 tablet afatinib single dose
treatment B	Experimental	Drug: ritonavir + afatinib2 x 2 tablets ritonavir for 3 days + 1 tablet afatinib on the second treatment day
treatment C	Experimental	Drug: ritonavir + afatinib2 x 2 tablets ritonavir for 3 days + 1 tablet afatinib on the second treatment day

Who may qualify

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

Key inclusion criteria (1 listed)

1. healthy male subjects

Key exclusion criteria (1 listed)

1. any relevant deviation from healthy conditions

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
afatinibstandard therapeutic dose	Drug	treatment A
ritonavir + afatinibsimultaneous intake of ritonavir and afatinib on second treatment day	Drug	treatment B
ritonavir + afatinibon the second treatment day the first ritonavir tablet will be taken 6 hours after the afatinib tablet	Drug	treatment C

Primary outcome

Area Under Curve From 0 to tz (AUC0-tz)
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
AUC0-tz represents the area under the concentration curve of the analyte in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte.
Maximum Concentration (Cmax)
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
Cmax represents the maximum concentration of the analyte in plasma.
Area Under Curve From 0 to ∞ Hours (AUC0-∞)
Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post
AUC0-∞ represents the area under the concentration curve of the analyte in plasma from 0 extrapolated to infinity.

Results and safety

Results posted to the registry on 19 Dec 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Participants	24	22

Primary outcome: Area Under Curve From 0 to tz (AUC0-tz)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Afatinib n = 21	Afatinib + Concomittant Rtv n = 24	Afatinib + Timed Rtv n = 22
Value	392 (26.2)	478 (27.9)	438 (20.3)

Afatinib vs Afatinib + Concomittant Rtv: Geometric mean ratio: 119.30 (90% CI 112.239 to 126.811), p = 0.1009, ANOVA
Afatinib vs Afatinib + Timed Rtv: Geometric mean ratio: 110.23 (90% CI 103.837 to 117.006), p = 0.0009, ANOVA
Afatinib + Concomittant Rtv vs Afatinib + Timed Rtv: Geometric mean ratio: 91.90 (90% CI 86.519 to 97.614), p = 0.0004, ANOVA

Population analysed: This subject set includes all evaluable subjects of the treated set who were assigned to the final dose groups and who provide at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.

Primary outcome: Maximum Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Afatinib n = 22	Afatinib + Concomittant Rtv n = 24	Afatinib + Timed Rtv n = 22
Value	19.5 (33.5)	20.7 (29.4)	20.7 (24.4)

Afatinib vs Afatinib + Concomittant Rtv: Geometric mean ratio: 104.06 (90% CI 96.681 to 112.002), p = 0.0002, ANOVA
Afatinib vs Afatinib + Timed Rtv: Geometric mean ratio: 105.09 (90% CI 96.425 to 114.530), p = 0.0012, ANOVA
Afatinib + Concomittant Rtv vs Afatinib + Timed Rtv: Geometric mean ratio: 99.75 (90% CI 93.328 to 106.610), p = 0.0000, ANOVA

Primary outcome: Area Under Curve From 0 to ∞ Hours (AUC0-∞)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Afatinib n = 22	Afatinib + Concomittant Rtv n = 24	Afatinib + Timed Rtv n = 22
Value	426 (22.8)	515 (27.5)	475 (19.4)

Afatinib vs Afatinib + Concomittant Rtv: Geometric mean ratio: 118.56 (90% CI 111.712 to 125.822), p = 0.0702, ANOVA
Afatinib vs Afatinib + Timed Rtv: Geometric mean ratio: 110.76 (90% CI 104.936 to 116.913), p = 0.0005, ANOVA
Afatinib + Concomittant Rtv vs Afatinib + Timed Rtv: Geometric mean ratio: 92.46 (90% CI 86.928 to 98.341), p = 0.0003, ANOVA

Adverse events

Time frame: First administration of trial medication until 28 days after last administration of trial medication. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Afatinib	0 of 23 (0%)	2 of 23 (8.7%)	Not reported
Afatinib + Concomittant Rtv	0 of 24 (0%)	7 of 24 (29.2%)	Not reported
Afatinib + Timed Rtv	0 of 22 (0%)	5 of 22 (22.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

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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.

Boehringer Ingelheim study chair

Boehringer Ingelheim

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 afatinib and ritonavir + afatinib in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

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 1 inclusion and 1 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 9 Jun 2014. 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 Germany. 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?

Yes. Results are posted in the registry (first posted 19 Dec 2013). 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?

Area Under Curve From 0 to tz (AUC0-tz) (time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post). The study lists 3 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 NCT01426958.

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 9 Jun 2014.