Clinical trial NCT05602597: HMPL-689 Drug Interaction Study With CYP3A Inhibitor/CYP2C9 Inhibitor/CYP3A Inducer/PPI
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed or Refractory Lymphoma
Keywords: Itraconazole
Fluconazole
Rifampin
Rabeprazole
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2022-11-02
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female between the ages of 18 and 55 years old (inclusive) at the time of informed consent.
2. Body mass index (BMI) \>18 and ≤29.9 kg/m2 at screening.
3. 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.
4. 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.
5. Must provide written informed consent prior to any study-specific screening procedures.
6. Willing and able to comply with all aspects of the protocol, as determined by the PI.

Exclusion Criteria:

1. 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.
2. Clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose.
3. 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).
4. Systolic blood of pressure \>140 mmHg or diastolic blood pressure of \> 90 mmHg.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Consumed grapefruit, starfruit, Seville oranges, or their products within 7 days prior to the first dose.
11. 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).
12. 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.
13. 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.
14. 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.
15. Allergic to any of the study drugs (or its excipients) to be given in this study.
16. Female healthy volunteer is pregnant, lactating, or breastfeeding.
17. Male healthy volunteer who plans to donate sperm or father a child within 30 days after receiving the study drug.
18. 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.
19. For Part A only, participants characterized by any of the following CYP2C9 genotypes: \*2/\*2, \*2/\*3, or \*3/\*3.

Primary outcomes:
measure: AUC0-t
timeFrame: From Day 1 to Day 11 (Day 12 for Rifampin)
measure: AUC0-inf
timeFrame: From Day 1 to Day 11 (Day 12 for Rifampin)
measure: Cmax
timeFrame: From Day 1 to Day 11 (Day 12 for Rifampin)
Secondary outcomes:
measure: Incidence of AEs/SAEs
timeFrame: From Day 1 to Day 11 (Day 12 for Rifampin)
Other outcomes:
Locations:
city: Miami
country: United States
facility: QPS- Miami
state: Florida
Study officials:
affiliation: Hutchmed
name: Vijay Jayaprakash, MD
role: STUDY_DIRECTOR
References: