Leukemia, Lymphocytic, Chronic, B-CellPhase 1NCT03301207
A Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Participants With B Cell Malignancy
A Phase 1 study testing Ibrutinib, OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg and Bupropion in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Janssen Research & Development, LLC at 4 sites in 2 countries.
Trial summary
The main purpose of this study is to evaluate the effects of repeat dosing of ibrutinib on the single-dose pharmacokinetics (PK) of oral contraceptives (OC - ethinylestradiol [EE] and levonorgestrel [LN]), the cytochrome P450 (CYP)2B6 probe bupropion and the CYP3A4 probe midazolam; and to evaluate the effects of… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell
- What is being tested?
- Ibrutinib, OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg and Bupropion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 20 Oct 2017to 4 Dec 2018
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or Waldenstrom's macroglobulinemia (WM)
- Participants with MCL must have relapsed or refractory disease after at least 1 prior line of systemic therapy
- Participants with MZL must have failed an anti-cluster of differentiation (CD)20 monoclonal antibody-based therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Adequate hematologic, hepatic, and renal functions
- Before the first dose of oral contraceptive (OC), a woman must be either:
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- Not of childbearing potential: postmenopausal (greater than [>]45 years of age with amenorrhea for at least 12 months and a serum follicle stimulating hormone level >40 international unit per Liter [IU/L] or milli international unit per milli Liter [mIU/mL]); permanently sterilized
- Of childbearing potential and practicing a highly effective non-hormonal method of birth control
- Women of childbearing potential must have a negative serum (Beta-human chorionic gonadotropin [Beta-hCG]) or urine pregnancy test at screening
Who cannot join
- Major surgery planned within 2 weeks of the first dose of ibrutinib or during study participation up to Cycle 2 Day 1
- History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present for greater than or equal to (>=)3 years before the first dose of ibrutinib and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated in-situ cancer without evidence of disease
- History of breast or endometrial cancer
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- Prior treatment/exposure with ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor
- Requires ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists (for example, phenprocoumon)
- Requires therapies that must be discontinued or substituted 7 days prior to Study Day 1, or must be temporally interrupted during the course of the study, including the following:
- Medications known to induce or inhibit drug metabolizing enzymes (CYP3A4 and CYP2B6)
- Medication which are not allowed to be used in combination with EE, LN, bupropion, or midazolam
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Poland2 sites
Pratia MCM Krakow
Krakow, 30-510
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
Wroclaw, 50-367
Spain2 sites
Hosp. Univ. Fund. Jimenez Diaz
Madrid, 28040
Clinica Univ. de Navarra
Pamplona, 31008
About this study
Official title: A Drug-Drug Interaction Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Subjects With B Cell Malignancy
The main purpose of this study is to evaluate the effects of repeat dosing of ibrutinib on the single-dose pharmacokinetics (PK) of oral contraceptives (OC - ethinylestradiol [EE] and levonorgestrel [LN]), the cytochrome P450 (CYP)2B6 probe bupropion and the CYP3A4 probe midazolam; and to evaluate the effects of single-dose ibrutinib on the single-dose PK of the CYP3A4 probe midazolam in female participants with B cell malignancy.
Read the detailed description
This is a multicenter study of ibrutinib (first-in-class, potent, covalently-binding inhibitor of Bruton's tyrosine kinase [BTK]) in female participants with B cell malignancy. The study consists of 3 phases: Screening Phase (up to 28 days), 7-day Pretreatment Phase (Days 1 to 7), Treatment Phase including PK assessment period (Days 8 to 26) and a Follow-up Phase (Day 27 to end of Cycle 6). The study procedures includes electrocardiogram (ECG), vital signs, blood samples withdrawal to evaluate PK and safety. The Antitumor activity will be assessed by means of computed tomography (CT) imaging and positron emission tomography (PET) scans. No formal statistical hypothesis will be tested. This is an estimation study designed to determine if an increase or decrease in exposure to OC or probe drugs occurs in the presence of ibrutinib.
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Being tested
- Ibrutinib, OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg, Bupropion, Midazolam
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
Ibrutinib capsule (at dose of 420 or 560 mg) will be taken orally QD.
OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcgDrug
Also called Microgynon 30
Single dose of oral contraceptives (OC) (1 tablet containing 30 mcg EE and 150 mcg LN) will be taken orally on Study Days 1 and 22.
BupropionDrug
Bupropion 75 mg tablet as a part of CYP cocktail will be taken on Study Days 3 and 24.
MidazolamDrug
Midazolam 2 mg (1 milliliter [mL]) oral solution will be taken on Study Days 3 and 24 (as a part of CYP cocktail) and on Study Day 8 (alone).
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib + Oral Contraceptives + Probe Drugs (CYP) | Experimental | Pre-treatment Phase: Participants will receive a single dose of oral contraceptive (OC) consisting of ethinylestradiol (EE) 30 microgram (mcg) and levonorgestrel (LN) 150 mcg on Study Day 1, and probe drugs (CYP) consisting of bupropion 75 milligram (mg) and midazolam 2 mg on Study Day 3, followed by a washout period from Study Days 4 to 7. Treatment Phase: Participants will receive ibrutinib 560 mg (4*140 mg capsules) once daily (QD) on Days 8 to 26 along with midazolam 2 mg once orally on Study Day 8 (Cycle 1 Day 1), OC once orally on Study Day 22 (Cycle 1 Day 15; EE and LN), and bupropion 75 mg and midazolam 2 mg once orally on Study Day 24 (Cycle 1 Day 17). From Study Day 27 (Cycle 1 Day 20) and onwards participants will continue oral treatment with ibrutinib 420 mg (3*140 mg capsules) or 560 mg QD (depending on the subtype of B-cell malignancy) up to the end of Cycle 6 (each cycle will consist of 28 days). Receives: Drug: Ibrutinib; Drug: OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg; Drug: Bupropion; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol (EE) and Levonorgestrel (LN) When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
The Cmax is the maximum observed plasma concentration.
Measured: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 hours (h) post-dose
Maximum Observed Plasma Concentration (Cmax) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
The Cmax is the maximum observed plasma concentration.
Measured: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose
Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib
The Cmax is the maximum observed plasma concentration.
Measured: Day 3: predose, 15 minutes (min), and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose
Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib
The Cmax is the maximum observed plasma concentration.
Measured: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of EE and LN When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Measured: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Measured: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Measured: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Measured: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of EE and LN When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Measured: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Measured: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Measured: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Measured: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose
Secondary outcomes (5)
Plasma Concentration of Ibrutinib and its Metabolite PCI-45227
Plasma concentrations of Ibrutinib and its Metabolite PCI-45227 will be measured.
Measured: Predose, 1, 2, 4, and 6 h post-dose on Days 8, 22, and 24
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Measured: Screening up to end of the 6 month treatment or 30 days after the last dose of study drug for Participants discontinuing treatment before 6 months
Number of Participants With Laboratory Abnormalities as a Measure of Safety and Tolerability
Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
Measured: Screening, Days 8 and 36, and End of Treatment (approximately 7 months)
Number of Participants With Electrocardiogram (ECG) Abnormalities Findings as a Measure of Safety and Tolerability
Triplicate ECG will be performed at screening and a single time point ECG will be performed at end of treatment visit.
Measured: Screening and End of Treatment (approximately 7 months)
Number of Participants With Vital Sign Abnormalities as a Measure of Safety and Tolerability
Vital signs includes Temperature, Heart Rate, Respiratory Rate and Blood Pressure.
Measured: Screening, Days 8 and 36, and End of Treatment (approximately 7 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2017
- Study start20 Oct 2017
- Primary completion17 Jul 2018
- Study completion4 Dec 2018
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 Leukemia, Lymphocytic, Chronic, B-CellStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03301207
- Sponsor's protocol ID
- CR108347
- Other IDs
- 2017-000496-84, 54179060CLL1017, 2017
- Status last verified
- Nov 2019
- First submitted
- 29 Sep 2017
- Last updated
- 5 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
de Jong J, Mitselos A, Jurczak W, Cordoba R, Panizo C, Wrobel T, Dlugosz-Danecka M, Jiao J, Sukbuntherng J, Ouellet D, Hellemans P. Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6. Pharmacol Res Perspect. 2020 Oct;8(5):e00649. doi: 10.1002/prp2.649.
PubMed 32945596
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Drug-Drug Interaction Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Subjects With B Cell Malignancy
- ClinicalTrials.gov ID
- NCT03301207
- Acronym / sponsor ID
- CR108347
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 20 Oct 2017 (actual)
- Primary completion
- 17 Jul 2018 (actual)
- Study completion
- 4 Dec 2018 (actual)
- First posted
- 4 Oct 2017 (actual)
- 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 main purpose of this study is to evaluate the effects of repeat dosing of ibrutinib on the single-dose pharmacokinetics (PK) of oral contraceptives (OC - ethinylestradiol [EE] and levonorgestrel [LN]), the cytochrome P450 (CYP)2B6 probe bupropion and the CYP3A4 probe midazolam; and to evaluate the effects of single-dose ibrutinib on the single-dose PK of the CYP3A4 probe midazolam in female participants with B cell malignancy.
Detailed description
This is a multicenter study of ibrutinib (first-in-class, potent, covalently-binding inhibitor of Bruton's tyrosine kinase [BTK]) in female participants with B cell malignancy. The study consists of 3 phases: Screening Phase (up to 28 days), 7-day Pretreatment Phase (Days 1 to 7), Treatment Phase including PK assessment period (Days 8 to 26) and a Follow-up Phase (Day 27 to end of Cycle 6). The study procedures includes electrocardiogram (ECG), vital signs, blood samples withdrawal to evaluate PK and safety. The Antitumor activity will be assessed by means of computed tomography (CT) imaging and positron emission tomography (PET) scans. No formal statistical hypothesis will be tested. This is an estimation study designed to determine if an increase or decrease in exposure to OC or probe drugs occurs in the presence of ibrutinib.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib + Oral Contraceptives + Probe Drugs (CYP) | Experimental | Drug: Ibrutinib, Drug: OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg, Drug: Bupropion, Drug: MidazolamPre-treatment Phase: Participants will receive a single dose of oral contraceptive (OC) consisting of ethinylestradiol (EE) 30 microgram (mcg) and levonorgestrel (LN) 150 mcg on Study Day 1, and probe drugs (CYP) consisting of bupropion 75 milligram (mg) and midazolam 2 mg on Study Day 3, followed by a washout period from Study Days 4 to 7. Treatment Phase: Participants will receive ibrutinib 560 mg (4*140 mg capsules) once daily (QD) on Days 8 to 26 along with midazolam 2 mg once orally on Study Day 8 (Cycle 1 Day 1), OC once orally on Study Day 22 (Cycle 1 Day 15; EE and LN), and bupropion 75 mg and midazolam 2 mg once orally on Study Day 24 (Cycle 1 Day 17). From Study Day 27 (Cycle 1 Day 20) and onwards participants will continue oral treatment with ibrutinib 420 mg (3*140 mg capsules) or 560 mg QD (depending on the subtype of B-cell malignancy) up to the end of Cycle 6 (each cycle will consist of 28 days). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or Waldenstrom's macroglobulinemia (WM)
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Adequate hematologic, hepatic, and renal functions
- Before the first dose of oral contraceptive (OC), a woman must be either:
- Women of childbearing potential must have a negative serum (Beta-human chorionic gonadotropin [Beta-hCG]) or urine pregnancy test at screening
Key exclusion criteria (11 listed)
- Major surgery planned within 2 weeks of the first dose of ibrutinib or during study participation up to Cycle 2 Day 1
- History of other malignancies, except:
- History of breast or endometrial cancer
- Prior treatment/exposure with ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor
- Requires ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists (for example, phenprocoumon)
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 |
|---|---|---|
| IbrutinibAlso: ImbruvicaIbrutinib capsule (at dose of 420 or 560 mg) will be taken orally QD. | Drug | Ibrutinib + Oral Contraceptives + Probe Drugs (CYP) |
| OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcgAlso: Microgynon 30Single dose of oral contraceptives (OC) (1 tablet containing 30 mcg EE and 150 mcg LN) will be taken orally on Study Days 1 and 22. | Drug | Ibrutinib + Oral Contraceptives + Probe Drugs (CYP) |
| BupropionBupropion 75 mg tablet as a part of CYP cocktail will be taken on Study Days 3 and 24. | Drug | Ibrutinib + Oral Contraceptives + Probe Drugs (CYP) |
| MidazolamMidazolam 2 mg (1 milliliter [mL]) oral solution will be taken on Study Days 3 and 24 (as a part of CYP cocktail) and on Study Day 8 (alone). | Drug | Ibrutinib + Oral Contraceptives + Probe Drugs (CYP) |
Primary outcome
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol (EE) and Levonorgestrel (LN) When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
Time frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 hours (h) post-dose
The Cmax is the maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
Time frame: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose
The Cmax is the maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib
Time frame: Day 3: predose, 15 minutes (min), and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose
The Cmax is the maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib
Time frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose
The Cmax is the maximum observed plasma concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of EE and LN When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
Time frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 h post-dose
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
Time frame: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib
Time frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib
Time frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of EE and LN When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
Time frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 h post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bupropion and 4-Hydroxybupropion When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone
Time frame: Days 3 and 24: predose, 0.5, 1, 2, 3, 4, 6, 10, 24, 34, 48, 58 h post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Repeat Doses of Ibrutinib
Time frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 24: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 24 h post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Midazolam and 1-Hydroxymidazolam When Co-Administered With Single Dose of Ibrutinib
Time frame: Day 3: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10,12, and 24 h post-dose; Day 8: predose, 15 min, and 0.5,1,2,3,4,5,6,8,10, and 12 h post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
5 secondary outcomes
Plasma Concentration of Ibrutinib and its Metabolite PCI-45227
Time frame: Predose, 1, 2, 4, and 6 h post-dose on Days 8, 22, and 24
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: Screening up to end of the 6 month treatment or 30 days after the last dose of study drug for Participants discontinuing treatment before 6 months
Number of Participants With Laboratory Abnormalities as a Measure of Safety and Tolerability
Time frame: Screening, Days 8 and 36, and End of Treatment (approximately 7 months)
Number of Participants With Electrocardiogram (ECG) Abnormalities Findings as a Measure of Safety and Tolerability
Time frame: Screening and End of Treatment (approximately 7 months)
Number of Participants With Vital Sign Abnormalities as a Measure of Safety and Tolerability
Time frame: Screening, Days 8 and 36, and End of Treatment (approximately 7 months)
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 5 Dec 2019.
- Derived from this study: PubMed 32945596de Jong J, Mitselos A, Jurczak W, Cordoba R, Panizo C, Wrobel T, Dlugosz-Danecka M, Jiao J, Sukbuntherng J, Ouellet D, Hellemans P. Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6. Pharmacol Res Perspect. 2020 Oct;8(5):e00649. doi: 10.1002/prp2.649.
- A Drug-Drug Interaction Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Subjects with B Cell MalignancyLink 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.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ibrutinib, OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg and Bupropion in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Janssen Research & Development, LLC at 4 sites in 2 countries.
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 9 inclusion and 11 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 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Poland, Spain. 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?
Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol (EE) and Levonorgestrel (LN) When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone (time frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 hours (h) post-dose). The study lists 12 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 NCT03301207, 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 5 Dec 2019.