Fungal InfectionPhase 1NCT04166669
A Drug-Drug Interaction Study of CYP3A4 Inhibition and Pan-CYP Induction on APX001
A Phase 1 study testing APX001, Itraconazole and Rifampin in people with Fungal Infection, run by Basilea Pharmaceutica at 2 sites in Netherlands.
Trial summary
This is a Phase 1, open-label study to evaluate the drug-drug interaction potential of a strong CYP3A4 inhibitor (itraconazole) and a pan-CYP inducer (rifampin) on APX001 in two parallel groups of healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Fungal Infection
- What is being tested?
- APX001, Itraconazole and Rifampin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesNetherlands
- Study dates
- 12 Nov 2019to 3 Mar 2020
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women must be postmenopausal or surgically sterile, or
- Women of childbearing potential must agree to avoid pregnancy during the study and to use contraception, or abstinence, at least 2 weeks before the start of study drug administration until 3 months after the last dose of study drug.
- Male subjects must agree to use barrier contraception, or commit to abstinence, from first Admission to the clinic until 3 months after the last dose of study drug.
- Body mass index (BMI): 18.0 to 32.0 kg/m sq, inclusive
- Weight: >= 50 kg
- Screening hematology, clinical chemistry, coagulation, and urinalysis consistent with overall good health
- Able to understand and comply with the requirements of the study, willing to return for all clinic visits, including confinement periods, and complete all study-related procedures Willing and able to provide written informed consent.
Who cannot join
- 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.
- 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.
- 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.
- 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.
- 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.
- Use of any prescription medication within 14 days prior to the planned first study drug administration and throughout the study (excluding female contraception).
Show all 21Show fewer
- Use of any non-prescription or over-the-counter medications within 7 days prior to the planned first study drug administration and throughout the study. This includes all vitamins, other herbal supplements, or remedies.
- Taking any drug or herbal CYP3A modulator (e.g. erythromycin; St. John's Wort) within 4 weeks (or 5 half-lives, whichever is longer) or any other nutrients known to modulate CYP3A activity (e.g. grapefruit juice; Seville orange) within 2 weeks prior to the first Admission.
- History of tobacco or any nicotine-containing product or device use within the past 3 months prior to the planned first study drug administration
- History of alcohol or substance abuse based on Investigator's judgment, within the past 12 months prior to the planned first study drug administration
- Concurrent social conditions (e.g. drugs-of-abuse, alcohol use of more than 24 units per week) that may potentially interfere with the subject's compliance with the protocol
- History of clinically significant allergic drug reactions
- Clinically significant physical examination, vital signs, laboratory safety test, or electrocardiogram (ECG) abnormalities
- Donation or loss of more than 100 mL of blood within 60 days prior to the first study drug administration. Donation or loss of more than 1.5 liters of blood (for male subjects) or more than 1.0 liter of blood (for female subjects) in the 10 months prior to the first study drug administration in the current study.
- Positive results on any of the following screening laboratory tests: serum pregnancy test, urine alcohol test, urine drugs-of-abuse (including cotinine), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV) antibody.
- Prior exposure to APX001
- Known allergy to corn or corn products or any inactive components of the study drug
- Known hypersensitivity to culprit drugs (itraconazole or rifampin).
- Additional Exclusion Criteria for Cohort 2:
- Diagnosis or suspected of having porphyria or having first-degree relatives diagnosed or suspected of having porphyria.
- Unwilling not to use contact lenses for the duration of rifampin dosing (Day 15 to Day 33 for Cohort 2) until 7 days after the last dose of rifampin (subjects in Cohort 2 may resume wearing contact lenses on Day 40).
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
PRA Health Sciences (PRA) - Early Development Services (EDS)
Groningen, 9728 NZ
PRA-EDS
Groningen
About this study
Official title: 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
This is a Phase 1, open-label study to evaluate the drug-drug interaction potential of a strong CYP3A4 inhibitor (itraconazole) and a pan-CYP inducer (rifampin) on APX001 in two parallel groups of healthy subjects.
- Conditions
- Fungal Infection
- Being tested
- APX001, Itraconazole, Rifampin
- Medical subject headings
- Mycoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APX001Drug
Also called Fosmanogepix
Cohort 1 Day 1: APX001 500 mg IV BID over a 3-hour infusion; Day 18: APX001 500 mg IV BID over a 3-hour infusion. Cohort 2 Day 1: APX001 1000 mg IV BID over a 3-hour infusion; Day 24: APX001 1000 mg IV BID over a 3-hour infusion.
ItraconazoleDrug
Also called Sporanox
Cohort 1 Days 15-30: itraconazole 200 mg oral solution QD.
RifampinDrug
Also called Rifampicin
Cohort 2 Days 15-33: rifampin 600 mg oral QD.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Drugs: APX001, itraconazole Receives: Drug: APX001; Drug: Itraconazole |
| Cohort 2 | Experimental | Drugs: APX001, rifampin Receives: Drug: APX001; Drug: Rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of APX001/APX001A as measured by area under the plasma concentration-time curve (AUC) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Measured: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by maximum observed plasma concentration (Cmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Measured: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by time to attain maximum observed plasma concentration (Tmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Measured: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by terminal elimination rate constant (λz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Measured: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by terminal elimination half-life (t1/2) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Measured: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by total clearance (CL) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Measured: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by the volume of distribution during the terminal phase (Vz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Measured: 6 weeks
Secondary outcomes (5)
Number of subjects experiencing and frequency of occurrence of adverse events as rated by CTCAE v5.0 after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Measured: 6 weeks
Occurrence and magnitude of clinical lab test values outside the normal range, clinically significant, and differing from baseline results after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
The following parameters will be measured:
- Clinical chemistry (serum quantitatively): total bilirubin, direct (conjugated) bilirubin, indirect (unconjugated) bilirubin (calculated), alkaline phosphatase, gamma-GT, ASAT, ALAT, LDH, p-amylase, lipase, CPK, creatinine, eGRF, urea, uric acid, cholesterol, triglycerides, total protein, albumin, globulin, glucose, inorganic phosphate, sodium, potassium, calcium, chloride, and bicarbonate.
- Hematology (blood quantitatively): leukocytes, erythrocytes, hemoglobin, hematocrit, thrombocytes, partial automated absolute differentiation: lymphocytes, monocytes, eosinophils, basophils, neutrophils, MCV, MCH, and MCHC.
- Coagulation (blood quantitatively): PT, aPTT, and fibrinogen.
- Urinalysis (urine qualitatively): color, protein, glucose, bilirubin, urobilinogen, ketones, blood, pH, specific gravity, and leukocytes.
Measured: 6 weeks
Occurrence of abnormal vital signs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Systolic and diastolic blood pressure and pulse will be recorded after the subject has been resting supine or semi-recumbent for at least 5 minutes. Body temperature and respiratory rate will be measured subsequently.
Measured: 6 weeks
Occurrence of abnormal, clinically significant results from 12-lead ECGs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
The following ECG parameters will be recorded: heart rate, PR interval, QRS duration, QT interval, and QTc interval (Fridericia's).
Measured: 6 weeks
Occurrence of changes in physical examinations which differ from baseline after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Physical examination will include: general appearance; skin/subcutaneous tissue; head; ears, nose, throat; neck and thyroid; thorax; lungs; cardiovascular; lymph nodes; abdomen; musculoskeletal; and neurological.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start12 Nov 2019
- Primary completion3 Mar 2020
- Study completion3 Mar 2020
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 Fungal InfectionStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Basilea Pharmaceutica
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marc Engelhardt, Study director, Basilea Pharmaceutica International Ltd, Allschwil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04166669
- Sponsor's protocol ID
- APX001-107
- Other IDs
- C4791007
- Status last verified
- May 2024
- First submitted
- 12 Nov 2019
- Last updated
- 17 May 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hodges MR, van Marle S, Kramer WG, Ople E, Tawadrous M, Jakate A. Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants. Antimicrob Agents Chemother. 2024 Jun 5;68(6):e0165023. doi: 10.1128/aac.01650-23. Epub 2024 May 17.
PubMed 38757982
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04166669
- Acronym / sponsor ID
- APX001-107
- Conditions
- Fungal Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Basilea PharmaceuticaIndustry (pharma, biotech, devices)
- Study start
- 12 Nov 2019 (actual)
- Primary completion
- 3 Mar 2020 (actual)
- Study completion
- 3 Mar 2020 (actual)
- First posted
- 18 Nov 2019 (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.
This is a Phase 1, open-label study to evaluate the drug-drug interaction potential of a strong CYP3A4 inhibitor (itraconazole) and a pan-CYP inducer (rifampin) on APX001 in two parallel groups of healthy subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: APX001, Drug: ItraconazoleDrugs: APX001, itraconazole |
| Cohort 2 | Experimental | Drug: APX001, Drug: RifampinDrugs: APX001, rifampin |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Women must be postmenopausal or surgically sterile, or
- Women of childbearing potential must agree to avoid pregnancy during the study and to use contraception, or abstinence, at least 2 weeks before the start of study drug administration until 3 months after the last dose of study drug.
- Male subjects must agree to use barrier contraception, or commit to abstinence, from first Admission to the clinic until 3 months after the last dose of study drug.
- Body mass index (BMI): 18.0 to 32.0 kg/m sq, inclusive
- Weight: >= 50 kg
Key exclusion criteria (21 listed)
- 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.
- 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.
- 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.
- 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.
- 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.
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 |
|---|---|---|
| APX001Also: FosmanogepixCohort 1 Day 1: APX001 500 mg IV BID over a 3-hour infusion; Day 18: APX001 500 mg IV BID over a 3-hour infusion. Cohort 2 Day 1: APX001 1000 mg IV BID over a 3-hour infusion; Day 24: APX001 1000 mg IV BID over a 3-hour infusion. | Drug | Cohort 1, Cohort 2 |
| ItraconazoleAlso: SporanoxCohort 1 Days 15-30: itraconazole 200 mg oral solution QD. | Drug | Cohort 1 |
| RifampinAlso: RifampicinCohort 2 Days 15-33: rifampin 600 mg oral QD. | Drug | Cohort 2 |
Primary outcome
Pharmacokinetics of APX001/APX001A as measured by area under the plasma concentration-time curve (AUC) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by maximum observed plasma concentration (Cmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by time to attain maximum observed plasma concentration (Tmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by terminal elimination rate constant (λz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by terminal elimination half-life (t1/2) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by total clearance (CL) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by the volume of distribution during the terminal phase (Vz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
5 secondary outcomes
Number of subjects experiencing and frequency of occurrence of adverse events as rated by CTCAE v5.0 after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Time frame: 6 weeks
Occurrence and magnitude of clinical lab test values outside the normal range, clinically significant, and differing from baseline results after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Time frame: 6 weeks
Occurrence of abnormal vital signs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Time frame: 6 weeks
Occurrence of abnormal, clinically significant results from 12-lead ECGs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Time frame: 6 weeks
Occurrence of changes in physical examinations which differ from baseline after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Time frame: 6 weeks
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 17 May 2024.
- Derived from this study: PubMed 38757982Hodges MR, van Marle S, Kramer WG, Ople E, Tawadrous M, Jakate A. Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants. Antimicrob Agents Chemother. 2024 Jun 5;68(6):e0165023. doi: 10.1128/aac.01650-23. Epub 2024 May 17.
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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.
Marc Engelhardt study director
Basilea Pharmaceutica International Ltd, Allschwil
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APX001, Itraconazole and Rifampin in people with Fungal Infection, run by Basilea Pharmaceutica at 2 sites in Netherlands.
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 7 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 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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?
Pharmacokinetics of APX001/APX001A as measured by area under the plasma concentration-time curve (AUC) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. (time frame: 6 weeks). The study lists 7 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 NCT04166669, 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 17 May 2024.