Relapsed or Refractory LymphomaPhase 1NCT05602597
HMPL-689 Drug Interaction Study With CYP3A Inhibitor/CYP2C9 Inhibitor/CYP3A Inducer/PPI
A Phase 1 study testing Itraconazole 200 mg, Fluconazole 400 mg and Rifampin 600 mg in people with Relapsed or Refractory Lymphoma, run by Hutchmed at 1 site in United States.
Trial summary
An open-label study to determine effect of Itraconazole, Fluconazole, Rifampin, and Rabeprazole on the PK of HMPL-689 Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Relapsed or Refractory Lymphoma
- What is being tested?
- Itraconazole 200 mg, Fluconazole 400 mg and Rifampin 600 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2022to 6 Aug 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female between the ages of 18 and 55 years old (inclusive) at the time of informed consent.
- Body mass index (BMI) >18 and ≤29.9 kg/m2 at screening.
- Females must be postmenopausal (defined as absence of menses for at least 1 year without alternative medical cause) or permanently sterile by total hysterectomy, bilateral oophorectomy, or bilateral salphingectomy.
- Males, including those who have had a successful vasectomy, must use a condom during sexual intercourse with women of childbearing potential starting from their first dose of study drug through 30 days after their last dose of study drug. Alternatively, abstinence is allowed if it is the normal and preferred lifestyle of the healthy volunteer.
- Must provide written informed consent prior to any study-specific screening procedures.
- Willing and able to comply with all aspects of the protocol, as determined by the PI.
Who cannot join
- Known history of any gastrointestinal surgery or any condition possibly affecting drug absorption (eg, cholecystectomy, gastrectomy, achlorhydria, peptic ulcer disease, history of stomach or intestinal surgery, or resection). Appendectomy and hernia repair are allowed.
- Clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose.
- Evidence of a clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations at screening or at Day -1 Check-in (baseline).
- Systolic blood of pressure >140 mmHg or diastolic blood pressure of > 90 mmHg.
- Clinically significant ECG abnormality, including a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTcF interval of > 450 msec), or had a family history of prolonged QTc syndrome or sudden death.
- History of smoking or use of nicotine containing substances within the previous 2 months, as determined by medical history or healthy volunteer's verbal report and confirmed by cotinine test at check in for each treatment period.
Show all 19Show fewer
- History of drug and/or alcohol misuse prior to screening or a positive urine drug test at Screening or at Check in for each treatment period.
- Diagnosed with acquired immune deficiency syndrome or has performed tests that are positive for human immunodeficiency virus, hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus, or pneumocystis jiroveci pneumonia.
- Participated in a clinical trial of other drug before screening, and the time since the last use of other study drug is less than 5 times the half-life or 4 weeks, whichever is longer, or the healthy volunteer is currently enrolled in another clinical study.
- Consumed grapefruit, starfruit, Seville oranges, or their products within 7 days prior to the first dose.
- Consumed herbal preparations/medications, including, but not limited to, St. John's Wort, kava, ephedra (ma huang), Ginkgo biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng, within 7 days prior to the first dose (21 days for St. John's Wort).
- Experienced a weight loss or gain of >10% within 4 weeks prior to the first dose as noted by medical history and weight at screening and Check-in.
- Received blood or blood products within 4 weeks or donated blood or blood products within 8 weeks prior to the first dose or donated double red cell within 16 weeks prior to first dose.
- Used any over-the-counter (OTC) medications or prescription drugs (medications that can inhibit or induce CYP3A4/CYPC9, or lower gastric acid in particular) within 2 weeks prior to the first dose.
- Allergic to any of the study drugs (or its excipients) to be given in this study.
- Female healthy volunteer is pregnant, lactating, or breastfeeding.
- Male healthy volunteer who plans to donate sperm or father a child within 30 days after receiving the study drug.
- Any condition that would make him or her, in the opinion of the PI or sponsor, unsuitable for the study, or who, in the opinion of the PI, is not likely to complete the study for any reason.
- For Part A only, participants characterized by any of the following CYP2C9 genotypes: *2/*2, *2/*3, or *3/*3.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-Label, 4-Part, Fixed-Sequence Study to Assess the Effect of Itraconazole, a Strong CYP3A Inhibitor, the Effect of Fluconazole, a Moderate CYP3A/2C9 Inhibitor, the Effect of Rifampin, a Strong CYP3A Inducer, and the Effect of Rabeprazole, a Proton Pump Inhibitor on the Pharmacokinetics of HMPL-689 in Healthy Volunteers
An open-label study to determine effect of Itraconazole, Fluconazole, Rifampin, and Rabeprazole on the PK of HMPL-689
Read the detailed description
A phase 1, open-label, 4-part, 2-period, fixed-sequence study to assess the effect of Itraconazole, a strong CYP3A inhibitor, the effect of Fluconazole, a moderate CYP3A/2C9 inhibitor, the effect of Rifampin, a strong CYP3A inducer, and the effect of Rabeprazole, a proton pump inhibitor on the pharmacokinetics (PK) of a single oral dose of HMPL-689 in study participants. The secondary objective is to evaluate the safety of a single oral dose of HMPL-689 administered with and without Itraconazole, Fluconazole, Rifampin, or Rabeprazole in study participants.
- Conditions
- Relapsed or Refractory Lymphoma
- Being tested
- Itraconazole 200 mg, Fluconazole 400 mg, Rifampin 600 mg, Rabeprazole 40 mg
- Keywords
- Itraconazole, Fluconazole, Rifampin, Rabeprazole
- Medical subject headings
- Recurrence, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Itraconazole 200 mgDrug
Study participants will be administered 200 mg itraconazole by mouth twice daily after the pharmacokinetic blood draw on Day 3 and once daily on Days 4 to 10, inclusive.
Fluconazole 400 mgDrug
Study participants will be administered 400 mg fluconazole by mouth daily on Day 3 after the pharmacokinetic blood draw, and 200 mg fluconazole by mouth daily on Days 4 to 10, inclusive.
Rifampin 600 mgDrug
Study participants will be administered 600 mg rifampin by mouth daily starting on Day 3, after the pharmacokinetic blood draw, and on Days 4 to 11, inclusive.
Rabeprazole 40 mgDrug
Study participants will be administered 40 mg rabeprazole by mouth daily on Day 3, after the pharmacokinetic blood draw, and on Days 4 to 9, inclusive.
| Study group | Role | What they receive |
|---|---|---|
| Part A - Itraconazole | Experimental | Period 1 -- Participants to receive 10mg dose of HMPL-689 by mouth as a single agent treatment on Day 1
Period 2 -- Participants to receive 200mg Itraconazole by mouth twice daily beginning on Day 3 through Day 10. On Day 7 200 mg Itraconazole and 10 mg HMPL-689 will be simultaneously administered. Receives: Drug: Itraconazole 200 mg |
| Part B - Fluconazole | Experimental | Period 1 -- Participants to receive 10mg dose of HMPL-689 by mouth as a single agent treatment on Day 1
Period 2 -- Participants to receive 400mg Fluconazole by mouth daily on Day 3, then 200 mg Fluconazole by mouth daily Day 4 through Day 10. On Day 7 200 mg Fluconazole and 10 mg HMPL-689 will be simultaneously administered. Receives: Drug: Fluconazole 400 mg |
| Part C - Rimfampin | Experimental | Period 1 -- Participants to receive 30mg dose of HMPL-689 by mouth as a single agent treatment on Day 1
Period 2 -- Participants to receive 600mg Rifampin by mouth daily beginning on Day 3 through Day 11. On Day 10 600mg Rifampin will be administered by mouth approximately 1 hour before the start of breakfast and 30mg HMPL-689 will be administered by mouth approximately 30 minutes after the start of breakfast. Receives: Drug: Rifampin 600 mg |
| Part D - Rabeprazole | Experimental | Period 1 -- Participants to receive 30mg dose of HMPL-689 by mouth as a single agent treatment on Day 1
Period 2 -- Participants to receive 40mg Rabeprazole by mouth daily beginning on Day 3 through Day 9. On Day 9 40mb Rabeprazole will be administered by mouth approximately 1 hour before the start of breakfast and 30mg HMPL-689 will be administered by mouth approximately 30 minutes after the start of breakfast. Receives: Drug: Rabeprazole 40 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC0-t
Area under the plasma concentration-time curve from time 0 to time of the last measurable concentration
Measured: From Day 1 to Day 11 (Day 12 for Rifampin)
AUC0-inf
Area under the plasma concentration-time curve from time 0 to infinity (if data permit)
Measured: From Day 1 to Day 11 (Day 12 for Rifampin)
Cmax
Maximum observed plasma concentration
Measured: From Day 1 to Day 11 (Day 12 for Rifampin)
Secondary outcomes (1)
Incidence of AEs/SAEs
Any untoward medical occurrence associated with the use of study drug
Measured: From Day 1 to Day 11 (Day 12 for Rifampin)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2022
- Study start1 Jun 2022
- Primary completion6 Aug 2022
- Study completion6 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory LymphomaStudies of the same condition, open and under way.
- More trials run by HutchmedThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vijay Jayaprakash, MD, Study director, Hutchmed
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05602597
- Sponsor's protocol ID
- 2021-689-00US1
- Status last verified
- Mar 2024
- First submitted
- 27 Oct 2022
- Last updated
- 6 Mar 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, 4-Part, Fixed-Sequence Study to Assess the Effect of Itraconazole, a Strong CYP3A Inhibitor, the Effect of Fluconazole, a Moderate CYP3A/2C9 Inhibitor, the Effect of Rifampin, a Strong CYP3A Inducer, and the Effect of Rabeprazole, a Proton Pump Inhibitor on the Pharmacokinetics of HMPL-689 in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05602597
- Acronym / sponsor ID
- 2021-689-00US1
- Conditions
- Relapsed or Refractory Lymphoma
- Keywords
- Itraconazole, Fluconazole, Rifampin, Rabeprazole
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 6 Aug 2022 (actual)
- Study completion
- 6 Aug 2022 (actual)
- First posted
- 2 Nov 2022 (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.
An open-label study to determine effect of Itraconazole, Fluconazole, Rifampin, and Rabeprazole on the PK of HMPL-689
Detailed description
A phase 1, open-label, 4-part, 2-period, fixed-sequence study to assess the effect of Itraconazole, a strong CYP3A inhibitor, the effect of Fluconazole, a moderate CYP3A/2C9 inhibitor, the effect of Rifampin, a strong CYP3A inducer, and the effect of Rabeprazole, a proton pump inhibitor on the pharmacokinetics (PK) of a single oral dose of HMPL-689 in study participants. The secondary objective is to evaluate the safety of a single oral dose of HMPL-689 administered with and without Itraconazole, Fluconazole, Rifampin, or Rabeprazole in study participants.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A - Itraconazole | Experimental | Drug: Itraconazole 200 mgPeriod 1 -- Participants to receive 10mg dose of HMPL-689 by mouth as a single agent treatment on Day 1 Period 2 -- Participants to receive 200mg Itraconazole by mouth twice daily beginning on Day 3 through Day 10. On Day 7 200 mg Itraconazole and 10 mg HMPL-689 will be simultaneously administered. |
| Part B - Fluconazole | Experimental | Drug: Fluconazole 400 mgPeriod 1 -- Participants to receive 10mg dose of HMPL-689 by mouth as a single agent treatment on Day 1 Period 2 -- Participants to receive 400mg Fluconazole by mouth daily on Day 3, then 200 mg Fluconazole by mouth daily Day 4 through Day 10. On Day 7 200 mg Fluconazole and 10 mg HMPL-689 will be simultaneously administered. |
| Part C - Rimfampin | Experimental | Drug: Rifampin 600 mgPeriod 1 -- Participants to receive 30mg dose of HMPL-689 by mouth as a single agent treatment on Day 1 Period 2 -- Participants to receive 600mg Rifampin by mouth daily beginning on Day 3 through Day 11. On Day 10 600mg Rifampin will be administered by mouth approximately 1 hour before the start of breakfast and 30mg HMPL-689 will be administered by mouth approximately 30 minutes after the start of breakfast. |
| Part D - Rabeprazole | Experimental | Drug: Rabeprazole 40 mgPeriod 1 -- Participants to receive 30mg dose of HMPL-689 by mouth as a single agent treatment on Day 1 Period 2 -- Participants to receive 40mg Rabeprazole by mouth daily beginning on Day 3 through Day 9. On Day 9 40mb Rabeprazole will be administered by mouth approximately 1 hour before the start of breakfast and 30mg HMPL-689 will be administered by mouth approximately 30 minutes after the start of breakfast. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male or female between the ages of 18 and 55 years old (inclusive) at the time of informed consent.
- Body mass index (BMI) >18 and ≤29.9 kg/m2 at screening.
- Females must be postmenopausal (defined as absence of menses for at least 1 year without alternative medical cause) or permanently sterile by total hysterectomy, bilateral oophorectomy, or bilateral salphingectomy.
- Males, including those who have had a successful vasectomy, must use a condom during sexual intercourse with women of childbearing potential starting from their first dose of study drug through 30 days after their last dose of study drug. Alternatively, abstinence is allowed if it is the normal and preferred lifestyle of the healthy volunteer.
- Must provide written informed consent prior to any study-specific screening procedures.
Key exclusion criteria (19 listed)
- Known history of any gastrointestinal surgery or any condition possibly affecting drug absorption (eg, cholecystectomy, gastrectomy, achlorhydria, peptic ulcer disease, history of stomach or intestinal surgery, or resection). Appendectomy and hernia repair are allowed.
- Clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose.
- Evidence of a clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations at screening or at Day -1 Check-in (baseline).
- Systolic blood of pressure >140 mmHg or diastolic blood pressure of > 90 mmHg.
- Clinically significant ECG abnormality, including a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTcF interval of > 450 msec), or had a family history of prolonged QTc syndrome or sudden death.
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 |
|---|---|---|
| Itraconazole 200 mgStudy participants will be administered 200 mg itraconazole by mouth twice daily after the pharmacokinetic blood draw on Day 3 and once daily on Days 4 to 10, inclusive. | Drug | Part A - Itraconazole |
| Fluconazole 400 mgStudy participants will be administered 400 mg fluconazole by mouth daily on Day 3 after the pharmacokinetic blood draw, and 200 mg fluconazole by mouth daily on Days 4 to 10, inclusive. | Drug | Part B - Fluconazole |
| Rifampin 600 mgStudy participants will be administered 600 mg rifampin by mouth daily starting on Day 3, after the pharmacokinetic blood draw, and on Days 4 to 11, inclusive. | Drug | Part C - Rimfampin |
| Rabeprazole 40 mgStudy participants will be administered 40 mg rabeprazole by mouth daily on Day 3, after the pharmacokinetic blood draw, and on Days 4 to 9, inclusive. | Drug | Part D - Rabeprazole |
Primary outcome
AUC0-t
Time frame: From Day 1 to Day 11 (Day 12 for Rifampin)
Area under the plasma concentration-time curve from time 0 to time of the last measurable concentration
AUC0-inf
Time frame: From Day 1 to Day 11 (Day 12 for Rifampin)
Area under the plasma concentration-time curve from time 0 to infinity (if data permit)
Cmax
Time frame: From Day 1 to Day 11 (Day 12 for Rifampin)
Maximum observed plasma concentration
1 secondary outcome
Incidence of AEs/SAEs
Time frame: From Day 1 to Day 11 (Day 12 for Rifampin)
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 6 Mar 2024.
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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.
Vijay Jayaprakash, MD study director
Hutchmed
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 Itraconazole 200 mg, Fluconazole 400 mg and Rifampin 600 mg in people with Relapsed or Refractory Lymphoma, run by Hutchmed 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 6 inclusion and 19 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 6 Mar 2024. 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?
AUC0-t (time frame: From Day 1 to Day 11 (Day 12 for Rifampin)). 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?
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 6 Mar 2024.