Nonhematologic MalignanciesPhase 1NCT01454076

Pharmacokinetics Study of Oral IXAZOMIB in Participants With Advanced Nonhematologic Malignancies or Lymphoma

A Phase 1 study testing Ixazomib 2.5 mg, Ixazomib 4 mg Capsule A and Ixazomib 4 mg Capsule B in people with Nonhematologic Malignancies and Lymphoma, run by Millennium Pharmaceuticals, Inc. at 1 site in United States.

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

This is an open-label, multicenter, sequential, 5-arm, phase 1 study of oral IXAZOMIB designed to assess drug-drug interaction with ketoconazole (Arm 1), the relative bioavailability of 2 capsule formulations of IXAZOMIB (Arm 2), food effect (Arm 3), drug-drug interaction with rifampin (Arm 4), and drug-drug… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Nonhematologic Malignancies, Lymphoma
What is being tested?: Ixazomib 2.5 mg, Ixazomib 4 mg Capsule A and Ixazomib 4 mg Capsule B
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 112 participants
Where: 1 siteUnited States
Study dates: 10 Nov 2011to 16 Jun 2016
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female participants 18 years or older.
Participants must have a diagnosis of histologically or cytologically confirmed metastatic and/or advanced solid tumor malignancy or lymphoma for which no effective standard treatment is available.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Female participants who are postmenopausal at least 1 year, or surgically sterile, or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time from the time of signing the consent form through 90 days after the last dose of study drug, or agree to practice true abstinence.
Male participants, even if surgically sterilized, agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug or agree to practice true abstinence.
Voluntary written informed consent.

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Clinical laboratory values as specified in protocol.
Suitable venous access.
Recovered (that is, less than [< ] Grade 1 toxicity or participant's baseline status) from the reversible effects of prior anticancer therapy.

Who cannot join

Peripheral neuropathy greater than (>) Grade 2 on clinical examination.
Systemic treatment with strong inhibitors of cytochrome P450 (CYP) 1A2, strong inhibitors of CYP3A, or strong CYP3A inducers or use of ginkgo biloba or St. John's wort within 14 days before the first dose of IXAZOMIB.
Participant has symptomatic brain metastasis. Participants with brain metastases must: have stable neurologic status following surgery or radiation for at least 2 weeks after completion of the definitive therapy; and be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Female participants who are pregnant or lactating.
Serious illness that could interfere with protocol completion.
Autologous stem cell transplant within 6 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.

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Prior treatment with rituximab or other unconjugated any antibody treatment within 42 days (21 days if there is clear evidence of progressive disease or immediate treatment is mandated).
Ongoing treatment with corticosteroids.
Radiotherapy within 21 days before the first dose of study drug.
Major surgery within 14 days before the first dose of study drug.
Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to first dose of study drug.
Life-threatening illness unrelated to cancer.
Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive, or suspected hepatitis C infection.
Diagnosis or treatment of another malignancy within 2 years preceding first dose, or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Evidence of uncontrolled cardiovascular conditions.
QTc > 500 milliseconds on a 12-lead electrocardiogram (ECG).
Known gastrointestinal disease or procedure that could interfere with the oral absorption or tolerance of IXAZOMIB including difficulty swallowing capsules; diarrhea > Grade 1 despite supportive therapy.
Participants with gastric achlorhydria (Arm 1 only).
Participants who have used any nicotine containing products within 14 days before the first dose of study drug (Arm 1, Arm 4, and Arm 5).
Treatment with any investigational products or systemic antineoplastic therapies within 21 days before the first dose of IXAZOMIB.
Participants with known hypersensitivity to macrolide antibiotics (example, clarithromycin, erythromycin, azithromycin) or a history of jaundice/liver injury during prior exposure to clarithromycin (Arm 5 only).

Trial locations and contacts

1 site in 1 country.

United States1 site

Study site
Dallas, Texas

Other trials in United States

About this study

Official title: A Phase 1 Study of Oral IXAZOMIB (MLN9708) to Assess Relative Bioavailability, Food Effect, Drug-Drug Interaction With Ketoconazole, Clarithromycin or Rifampin; and Safety and Tolerability in Patients With Advanced Nonhematologic Malignancies or Lymphoma

Conditions: Nonhematologic Malignancies, Lymphoma
Being tested: Ixazomib 2.5 mg, Ixazomib 4 mg Capsule A, Ixazomib 4 mg Capsule B, Ketoconazole, Rifampin
Keywords: Cmax: maximum plasma concentration, AUC0-tlast: area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
Medical subject headings: Lymphoma

What participants receive

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

Ixazomib 2.5 mgDrug
Ixazomib 2.5 mg Capsule B (Cycle 1 only)
Ixazomib 4 mg Capsule ADrug
Ixazomib 4 mg Capsule A (Cycle 1 only)
Ixazomib 4 mg Capsule BDrug
Ixazomib 4 mg Capsule B (Cycle 2 and beyond )
KetoconazoleDrug
Ketoconazole 400 mg tablets (Cycle 1 only)
RifampinDrug
Rifampin 600 mg capsule (Cycle 1 only)
ClarithromycinDrug
Clarithromycin 500 mg tablets (Cycle 1 only)
Ixazomib 4 mg Capsule BDrug
Ixazomib 4 mg Capsule B (Cycle 1 and beyond)

Study groups in NCT01454076
Study group	Role	What they receive
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg	Experimental	Ixazomib 2.5 milligram (mg), capsule B, orally, once on Day 1 and 15 along with ketoconazole 400 mg, tablets, orally, once daily from Day 12 to 25 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. Receives: Drug: Ixazomib 2.5 mg; Drug: Ixazomib 4 mg Capsule B; Drug: Ketoconazole
Arm 2: Ixazomib 4 mg Capsule A or B	Experimental	Ixazomib 4 mg, capsule A, orally, once on Day 1 followed by ixazomib 4 mg, capsule B once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, once on Day 1 followed by ixazomib 4 mg, capsule A once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. Receives: Drug: Ixazomib 4 mg Capsule A; Drug: Ixazomib 4 mg Capsule B
Arm 3: Ixazomib 4 mg Fasted or Fed	Experimental	Ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fed state, once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, under fed state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. Receives: Drug: Ixazomib 4 mg Capsule B
Arm 4: Ixazomib 4 mg + Rifampin 600 mg	Experimental	Ixazomib, 4 mg, capsule B, orally, once on Day 8 along with rifampin 600 mg, capsule, orally, once daily from Day 1 to 14 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. Receives: Drug: Rifampin; Drug: Ixazomib 4 mg Capsule B
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg	Experimental	Ixazomib, 2.5 mg, capsule B, orally, once on Day 6 along with clarithromycin, 500 mg, tablet, orally, twice daily from Day 1 to 16 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. Receives: Drug: Ixazomib 2.5 mg; Drug: Ixazomib 4 mg Capsule B; Drug: Clarithromycin

What is being measured

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

Cmax: Maximum Observed Plasma Concentration for Ixazomib
Measured: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Measured: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Measured: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose

Secondary outcomes (4)

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45)
Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities
Measured: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
Number of Participants With Clinically Significant Vital Sign Abnormalities
Measured: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
Percentage of Participants With Best Overall Response
Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: Complete response (CR) was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 millimeter [mm]). No new lesions. Partial response (PR) was defined as greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD) was defined as not qualifying for CR, PR, Progressive Disease (PD). An increase of >=20% from the nadir (or baseline, if it represents the point at which the sum of target disease was lowest) represents PD.
Measured: Baseline up to end of treatment (approximately 1.9 years)

Timeline

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

10 Nov 201116 Jun 2016

First posted18 Oct 2011 (estimated)
Study start10 Nov 2011
Primary completion1 Apr 2015
Study completion16 Jun 2016

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.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Nonhematologic MalignanciesStudies 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: Sequential
Masking: None (open label)
Enrolment: 112 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01454076
Sponsor's protocol ID: C16009
Other IDs: U1111-1183-0218
Status last verified: Jun 2017
First submitted: 13 Oct 2011
Last updated: 1 Nov 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Gupta N, Hanley MJ, Venkatakrishnan K, Bessudo A, Rasco DW, Sharma S, O'Neil BH, Wang B, Liu G, Ke A, Patel C, Rowland Yeo K, Xia C, Zhang X, Esseltine DL, Nemunaitis J. Effects of Strong CYP3A Inhibition and Induction on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor: Results of Drug-Drug Interaction Studies in Patients With Advanced Solid Tumors or Lymphoma and a Physiologically Based Pharmacokinetic Analysis. J Clin Pharmacol. 2018 Feb;58(2):180-192. doi: 10.1002/jcph.988. Epub 2017 Aug 11.
PubMed 28800141
Hanley MJ, Gupta N, Venkatakrishnan K, Bessudo A, Sharma S, O'Neil BH, Wang B, van de Velde H, Nemunaitis J. A Phase 1 Study to Assess the Relative Bioavailability of Two Capsule Formulations of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. J Clin Pharmacol. 2018 Jan;58(1):114-121. doi: 10.1002/jcph.987. Epub 2017 Aug 7.
PubMed 28783865
Gupta N, Hanley MJ, Venkatakrishnan K, Wang B, Sharma S, Bessudo A, Hui AM, Nemunaitis J. The Effect of a High-Fat Meal on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. J Clin Pharmacol. 2016 Oct;56(10):1288-95. doi: 10.1002/jcph.719. Epub 2016 Mar 17.
PubMed 26872892

Study at a glance

From the registry record, last updated by the sponsor on 1 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study of Oral IXAZOMIB (MLN9708) to Assess Relative Bioavailability, Food Effect, Drug-Drug Interaction With Ketoconazole, Clarithromycin or Rifampin; and Safety and Tolerability in Patients With Advanced Nonhematologic Malignancies or Lymphoma
ClinicalTrials.gov ID: NCT01454076
Acronym / sponsor ID: C16009
Conditions: Nonhematologic Malignancies, Lymphoma
Keywords: Cmax: maximum plasma concentration, AUC0-tlast: area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 112 participants (actual)
Lead sponsor: Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 10 Nov 2011 (actual)
Primary completion: 1 Apr 2015 (actual)
Study completion: 16 Jun 2016 (actual)
First posted: 18 Oct 2011 (estimated)
Results: Posted 1 Nov 2017

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg	Experimental	Drug: Ixazomib 2.5 mg, Drug: Ixazomib 4 mg Capsule B, Drug: KetoconazoleIxazomib 2.5 milligram (mg), capsule B, orally, once on Day 1 and 15 along with ketoconazole 400 mg, tablets, orally, once daily from Day 12 to 25 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.
Arm 2: Ixazomib 4 mg Capsule A or B	Experimental	Drug: Ixazomib 4 mg Capsule A, Drug: Ixazomib 4 mg Capsule BIxazomib 4 mg, capsule A, orally, once on Day 1 followed by ixazomib 4 mg, capsule B once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, once on Day 1 followed by ixazomib 4 mg, capsule A once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.
Arm 3: Ixazomib 4 mg Fasted or Fed	Experimental	Drug: Ixazomib 4 mg Capsule BIxazomib 4 mg, capsule B, orally, under fasted state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fed state, once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, under fed state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.
Arm 4: Ixazomib 4 mg + Rifampin 600 mg	Experimental	Drug: Rifampin, Drug: Ixazomib 4 mg Capsule BIxazomib, 4 mg, capsule B, orally, once on Day 8 along with rifampin 600 mg, capsule, orally, once daily from Day 1 to 14 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg	Experimental	Drug: Ixazomib 2.5 mg, Drug: Ixazomib 4 mg Capsule B, Drug: ClarithromycinIxazomib, 2.5 mg, capsule B, orally, once on Day 6 along with clarithromycin, 500 mg, tablet, orally, twice daily from Day 1 to 16 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Male or female participants 18 years or older.
Participants must have a diagnosis of histologically or cytologically confirmed metastatic and/or advanced solid tumor malignancy or lymphoma for which no effective standard treatment is available.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Female participants who are postmenopausal at least 1 year, or surgically sterile, or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time from the time of signing the consent form through 90 days after the last dose of study drug, or agree to practice true abstinence.
Male participants, even if surgically sterilized, agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug or agree to practice true abstinence.

Key exclusion criteria (21 listed)

Peripheral neuropathy greater than (>) Grade 2 on clinical examination.
Systemic treatment with strong inhibitors of cytochrome P450 (CYP) 1A2, strong inhibitors of CYP3A, or strong CYP3A inducers or use of ginkgo biloba or St. John's wort within 14 days before the first dose of IXAZOMIB.
Participant has symptomatic brain metastasis. Participants with brain metastases must: have stable neurologic status following surgery or radiation for at least 2 weeks after completion of the definitive therapy; and be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Female participants who are pregnant or lactating.
Serious illness that could interfere with protocol completion.

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
Ixazomib 2.5 mgIxazomib 2.5 mg Capsule B (Cycle 1 only)	Drug	Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg, Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg
Ixazomib 4 mg Capsule AIxazomib 4 mg Capsule A (Cycle 1 only)	Drug	Arm 2: Ixazomib 4 mg Capsule A or B
Ixazomib 4 mg Capsule BIxazomib 4 mg Capsule B (Cycle 2 and beyond )	Drug	Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg, Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg
KetoconazoleKetoconazole 400 mg tablets (Cycle 1 only)	Drug	Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg
RifampinRifampin 600 mg capsule (Cycle 1 only)	Drug	Arm 4: Ixazomib 4 mg + Rifampin 600 mg
ClarithromycinClarithromycin 500 mg tablets (Cycle 1 only)	Drug	Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg
Ixazomib 4 mg Capsule BIxazomib 4 mg Capsule B (Cycle 1 and beyond)	Drug	Arm 2: Ixazomib 4 mg Capsule A or B, Arm 3: Ixazomib 4 mg Fasted or Fed, Arm 4: Ixazomib 4 mg + Rifampin 600 mg

Primary outcome

Cmax: Maximum Observed Plasma Concentration for Ixazomib
Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose

4 secondary outcomes

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45)
Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities
Time frame: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
Number of Participants With Clinically Significant Vital Sign Abnormalities
Time frame: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
Percentage of Participants With Best Overall Response
Time frame: Baseline up to end of treatment (approximately 1.9 years)

Results and safety

Results posted to the registry on 1 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg	29	16
Arm 2: Ixazomib 4 mg Capsule A or B	20	14
Arm 3: Ixazomib 4 mg Fasted or Fed	24	15
Arm 4: Ixazomib 4 mg + Rifampin 600 mg	18	16
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg	21	15

Primary outcome: Cmax: Maximum Observed Plasma Concentration for Ixazomib

Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose. Geometric mean (Standard Deviation). Unit: nanogram per milliliter (ng/mL)

Measure	Arm 1: Ixazomib 2.5 mg n = 16	Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg n = 16	Arm 2: Ixazomib 4 mg Capsule A n = 14	Arm 2: Ixazomib 4 mg Capsule B n = 14	Arm 3: Ixazomib 4 mg Fasted n = 15	Arm 3: Ixazomib 4 mg Fed n = 15	Arm 4: Ixazomib 4 mg + Rifampin 600 mg n = 16	Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg n = 15
Value	38.975 (21.3727)	39.250 (27.3318)	61.866 (48.3909)	71.949 (46.2132)	77.001 (53.5905)	22.752 (15.0506)	25.706 (15.1435)	37.245 (21.4416)

Population analysed: The pharmacokinetic (PK)-evaluable population included all participants who received protocol-specified dose in Cycle 1 without dose reductions/interruptions, did not receive any excluded concomitant medication during PK sampling, and had sufficient concentration-time data to permit estimation of PK parameters by noncompartmental analysis methods.

Primary outcome: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib

Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose. Geometric mean (Standard Deviation). Unit: nanogram*hour per milliliter (ng*hr/mL)]

Measure	Arm 1: Ixazomib 2.5 mg n = 16	Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg n = 16	Arm 2: Ixazomib 4 mg Capsule A n = 14	Arm 2: Ixazomib 4 mg Capsule B n = 14	Arm 3: Ixazomib 4 mg Fasted n = 15	Arm 3: Ixazomib 4 mg Fed n = 15	Arm 4: Ixazomib 4 mg + Rifampin 600 mg n = 16	Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg n = 15
Value	551.985 (191.4490)	1148.778 (581.4376)	1284.079 (941.4838)	1334.659 (1244.0951)	1465.979 (812.0514)	998.698 (1019.1868)	231.527 (134.9720)	613.112 (375.0216)

Population analysed: The PK-evaluable population included all participants who received protocol-specified dose in Cycle 1 without dose reductions/interruptions, did not receive any excluded concomitant medication during PK sampling, and had sufficient concentration-time data to permit estimation of PK parameters by noncompartmental analysis methods.

Primary outcome: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

Measure	Arm 1: Ixazomib 2.5 mg n = 16	Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg n = 16	Arm 2: Ixazomib 4 mg Capsule A n = 14	Arm 2: Ixazomib 4 mg Capsule B n = 14	Arm 3: Ixazomib 4 mg Fasted n = 15	Arm 3: Ixazomib 4 mg Fed n = 15	Arm 4: Ixazomib 4 mg + Rifampin 600 mg n = 16	Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg n = 15
Value	1.090 (0.47 to 2.07)	1.500 (0.50 to 4.17)	1.290 (0.52 to 3.00)	1.250 (0.50 to 7.50)	1.020 (0.48 to 4.00)	4.000 (1.93 to 8.03)	1.450 (0.50 to 4.12)	1 (0.42 to 7.18)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events are adverse events that started after first dose of study drug and no more than 30 days for a serious adverse event after last dose of study drug (Cycle 25 Day 45). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg	12 of 29 (41.4%)	28 of 29 (96.6%)	Not reported
Arm 2: Ixazomib 4 mg Capsule A or B	5 of 20 (25%)	20 of 20 (100%)	Not reported
Arm 3: Ixazomib 4 mg Fasted or Fed	12 of 24 (50%)	23 of 24 (95.8%)	Not reported
Arm 4: Ixazomib 4 mg + Rifampin 600 mg	3 of 18 (16.7%)	18 of 18 (100%)	Not reported
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg	10 of 21 (47.6%)	20 of 21 (95.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28800141Gupta N, Hanley MJ, Venkatakrishnan K, Bessudo A, Rasco DW, Sharma S, O'Neil BH, Wang B, Liu G, Ke A, Patel C, Rowland Yeo K, Xia C, Zhang X, Esseltine DL, Nemunaitis J. Effects of Strong CYP3A Inhibition and Induction on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor: Results of Drug-Drug Interaction Studies in Patients With Advanced Solid Tumors or Lymphoma and a Physiologically Based Pharmacokinetic Analysis. J Clin Pharmacol. 2018 Feb;58(2):180-192. doi: 10.1002/jcph.988. Epub 2017 Aug 11.
Derived from this study: PubMed 28783865Hanley MJ, Gupta N, Venkatakrishnan K, Bessudo A, Sharma S, O'Neil BH, Wang B, van de Velde H, Nemunaitis J. A Phase 1 Study to Assess the Relative Bioavailability of Two Capsule Formulations of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. J Clin Pharmacol. 2018 Jan;58(1):114-121. doi: 10.1002/jcph.987. Epub 2017 Aug 7.
Derived from this study: PubMed 26872892Gupta N, Hanley MJ, Venkatakrishnan K, Wang B, Sharma S, Bessudo A, Hui AM, Nemunaitis J. The Effect of a High-Fat Meal on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. J Clin Pharmacol. 2016 Oct;56(10):1288-95. doi: 10.1002/jcph.719. Epub 2016 Mar 17.

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.

Medical Monitor study director

Millennium Pharmaceuticals, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 21 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 1 Nov 2017. 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?

Yes. Results are posted in the registry (first posted 1 Nov 2017). 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?

Cmax: Maximum Observed Plasma Concentration for Ixazomib (time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose). 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 NCT01454076, which also lists 3 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 1 Nov 2017.