A phase 1, open-label, fixed-sequence, drug-drug interaction study of APX001 to evaluate the effects of CYP3A4 inhibition and pan-CYP induction in two parallel groups of healthy male and female subjects
- Conditions
- Fungal infections
- Registration Number
- NL-OMON47992
- Lead Sponsor
- Amplyx Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 36
1. Healthy male or female subjects, aged 18 to 60 years inclusive at Screening.
- Women must be postmenopausal or surgically sterile, or
- Women of childbearing potential, with a fertile male sexual partner, must
agree to avoid pregnancy during the study and to use 2 methods of birth control
(using hormonal contraceptives or an intrauterine device combined with at least
1 of the following forms of contraception: a diaphragm or cervical cap, or a
condom) at least 2 weeks before the start of study drug administration (as long
as on one effective method for at least 3 cycles prior to dosing), or
abstinence, which is considered an effective method if it is defined as a
lifestyle preference (refraining from heterosexual intercourse) for the
duration of study participation, and for 3 months after the last dose of study
drug. At Screening and at Admission on Day -1, female subjects must be
nonpregnant and nonlactating.
- Male subjects with partner(s) of childbearing potential must agree to use
appropriate barrier contraception to avoid fathering a child from first
Admission to the clinical research unit until 3 months after receiving the last
dose of study drug. They must commit to abstinence from heterosexual
intercourse, or agree to use appropriate barrier contraception, and the use of
hormonal contraceptives or an intrauterine device by the female partner. Male
subjects must not donate sperm from first Admission to the clinical research
unit until 3 months after receiving the last dose of study drug.
2. Body mass index (BMI) : 18.0 to 32.0 kg/m2, inclusive.
3. Weight : >=50 kg.
4. Screening hematology, clinical chemistry, coagulation, and urinalysis
consistent with overall good health and the following criteria are met:
- Creatinine within normal limits.
- Estimated (Chronic Kidney Disease Epidemiology Collaboration equation)
creatinine clearance within normal limits.
5. Able to understand and comply with the requirements of the study, willing to
return for all clinic visits, including the confinement periods, and complete
all study-related procedures.
6. Willing and able to provide written informed consent.
1. Having any uncontrolled or active major systemic disease including, but not
limited to: cardiovascular, pulmonary, gastrointestinal, metabolic, urogenital,
neurological, immunological, psychiatric, or neoplastic disorder with
metastatic potential.
2. History or presence of malignancy within the past year. Subjects who have
been successfully treated with no recurrence of basal cell carcinoma of the
skin or carcinoma in-situ of the cervix may be enrolled.
3. Active acute or chronic infection, including, but not limited to: upper
airway infection, urinary tract infection, or skin infection within 30 days
preceding entry into the study.
4. Significant and/or acute illness within 5 days prior to the first study drug
administration that may impact safety assessments, in the opinion of the
Investigator.
5. Participation in an investigational drug study within 60 days prior to the
first study drug administration in the current study. Participation in more
than 3 other drug studies in the 10 months prior to the first study drug
administration in the current study.
Further criteria apply
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Cohort 1<br /><br>The effects of multiple doses of a CYP3A4 inhibitor, itraconazole (oral<br /><br>solution), on the PK of APX001 and APX001A, following IV administration of 500<br /><br>mg APX001 (as a 3-hour infusion) bid for 1 day, with a dosing interval of<br /><br>approximately 9 hours.<br /><br><br /><br>Cohort 2<br /><br>The effects of multiple doses of a pan-CYP inducer, oral rifampin, on the PK of<br /><br>APX001 and APX001A, following IV administration of 1000 mg APX001 (as a 3-hour<br /><br>infusion) bid for 1 day, with a dosing interval of approximately 9 hours.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Cohort 1<br /><br>Safety and tolerability of an IV dose (500 mg as a 3-hour infusion bid for 1<br /><br>day, with a dosing interval of approximately 9 hours) of APX001 alone and when<br /><br>co-administered with itraconazole (oral solution).<br /><br><br /><br>Cohort 2<br /><br>Safety and tolerability of an IV dose (1000 mg as a 3-hour infusion bid for 1<br /><br>day, with a dosing interval of approximately 9 hours) of APX001 alone and when<br /><br>co-administered with oral rifampin.</p><br>