- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07580833
A Study to Investigate the Effect of Food on the Bioavailability of Oral Paclitaxel Administered With Encequidar in Participants With Advanced Solid Tumors
The goal of this clinical trial is to learn about the effect of food on absorption of oral Paclitaxel when co- administered with Encequidar tablets in adult patients with tumours.
The main questions it aims to answer are:
- The effect of food and fasting on absorption of oral paclitaxel when combined with Encequidar tablets
- Assessment of safety and tolerability of oral paclitaxel when combined with Encequidar tablets
Participants will take Encequidar and oral paclitaxcel with a 1-hour space in between, either after an overnight fast of 10hours or after a meal three days in a row. After 10 days participants that received paclitaxel after fasting will receive the same medicine in the same way after a meal and vice versa. Some participants can elect to take part in the third part of the study which involves taking both paclitaxel and encequidar at the same time after a meal.
Participants will
- For parts 1,2 and 3 participants will stay at the clinic from the day before the study starts until day 4 to receive the medicine and participate in checkups and tests. Participants will then visit the clinic on day 6 and 8 for further checkups and tests
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Study Design:
This is a randomized, balanced, multidose, 2-period, two-way (i.e., fed versus fasted), crossover design to examine the effect of food on paclitaxel bioavailability when administered as oPac+E to eligible participants. After completion of the two-way cross over periods, a subset of participants will receive concurrent encequidar and oral paclitaxel capsules after a low-fat meal in Period 3, which is a nonrandomized single arm. Following the Food Effect Part, continued treatment will be offered in the Treatment Part of the study for all participants who complete the Food Effect Part.
In the Food Effect Part (two-way crossover), approximately 46 participants will be randomized. After participants have finished Period 2, they will be asked if they feel comfortable entering Period 3. Enrollment of participants into Period 3 will stop after 8 participants have been enrolled. In the Food Effect Part, an unexpected serious adverse reaction that results in death will be used as stopping criteria for safety that will trigger suspension of enrollment to allow for a detailed safety review. Participants who do not participate in Period 3 will enter into the Treatment Part following Period 2. The Food Effect Part will include Screening, Baseline, Treatment, and safety follow-up.
Food Effect Part:
In the Food Effect Part (randomized 2-period, two-way crossover), participants will receive oPac+E in 2 sequences (fed/fasted or fasted/fed) in which encequidar is administered 1 hour before the oral paclitaxel capsules. A treatment of oPac+E consisting of 3 daily doses will be administered on 3 consecutive days in each period. In Period 3, participants will receive concurrent administration of encequidar and oral paclitaxel after a low-fat meal. As patients with metastatic cancer frequently have decreased appetite and may have difficulty eating a high-fat meal, the Food Effect Part will be conducted using the Food and Drug Administration (FDA) recommended low-fat meal as per the FDA Guidance for Industry "Assessing the Effects of Food on Drugs in INDs and NDAs - Clinical Pharmacology Considerations 2022". Participants will be randomized to the sequence under which they will be administered oPac+E following an overnight fast of at least 10 hours. In each period, participants will be housed in the clinic from Day -1 until after collection of the 72-hour PK sample on Day 4. Participants will then return to the clinic for additional PK sample collections at designated time points on Days 6 and 8. There will be a washout of at least 10 days after the last dose between periods to minimize carryover, based on the estimated half-life (43 hours) of paclitaxel. The oral paclitaxel dose should remain unchanged (total mg dose) during the Food Effect Part of the trial. Period 2 may be delayed up to 3 weeks to allow recovery from toxicity which interrupted treatment or up to 4 weeks to allow flexibility to schedule inpatient treatment. A final visit will occur on the last day of PK sampling or up to 2 weeks after the end of PK sampling.
Period 3 will begin at least 10 days after the last dose in Period 2. Participants will be housed in the clinic from Day -1 until after collection of the 72 hours PK sample on Day 4. Participants will then return to the clinic for additional PK sample collections at designated time points on Days 6 and 8. A final visit will occur on the last day of PK sampling or up to 2 weeks after the end of PK sampling. Participants who discontinue prior to completion of the Food Effect Part will be followed for ongoing or new AE/SAEs until 30 days after the last dose or resolution/stabilization. Participants who successfully complete the Food Effect Part will be offered treatment with oPac+E in the Treatment Part of this protocol to further evaluate oPac+E safety.
Treatment Part:
In the Treatment Part, oPac+E will be administered on an empty stomach at a dose of 205 mg/m2/day for 3 consecutive days per week for 3 weeks of a 4-week cycle, a dose and regimen being used in the ongoing oPac+E development program. Participants who experience toxicity may continue treatment with dose modifications (dose reduction, dose delay) as allowed during management of common paclitaxel toxicity, if considered appropriate by the investigator. oPac+E treatment will be discontinued in participants who did not recover within 3 weeks from oral paclitaxel toxicity that interrupted treatment. Participants in the Treatment Part will continue receiving cycles of treatment until they meet protocol-specified discontinuation criteria or the investigator is of the opinion that the participant is no longer benefitting from treatment and enter the safety follow-up. CT scans will be performed for surveillance of disease every 8 weeks. oPac+E treatment will be stopped if there is disease progression. During the safety follow-up, participants will be followed for 30 days after their last dose. A final visit will occur at the last clinic visit or up to 30 days after the last dose administered.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 1
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
Inclusion Criteria:
- Signed written informed consent
- ≥18 years of age
- Cancer patients for whom treatment with paclitaxel monotherapy is a reasonable therapeutic option, including but not limited to: advanced or metastatic breast cancer, gastric cancer (who have not undergone gastric resection surgery), non-small cell lung cancer, or ovarian cancer.
- Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective and for which oral paclitaxel is a reasonable treatment. Participants who are intolerant of standard-of-care treatment or declined standard-of-care treatment may be enrolled.
Adequate hematologic status as demonstrated by not requiring granulocyte colony stimulating factor (G-CSF) or transfusion support within 30 days prior to randomization to achieve the following at Screening/Baseline:
- Absolute neutrophil count (ANC) ≥1.5 × 109/L
- Platelet count ≥100 × 109/L
- Hemoglobin ≥10 g/dL
Adequate liver function at Screening/Baseline as demonstrated by:
- Total bilirubin ≤ upper limit of normal (ULN) unless the participant has documented Gilbert's disease, for which bilirubin must be ≤2.0 × ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 × ULN
- Adequate renal function at Screening/Baseline as demonstrated by estimated glomerular filtration rate (eGFR) ≥60 mL/min.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Able to fast for 10 hours before and 4 hours after oPac+E administration.
- Women must be postmenopausal (≥12 months without menses) or surgically sterile (i.e. by hysterectomy and/or bilateral oophorectomy) or, must be using effective contraception (i.e. non hormonal intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 4 months after their last dose of study drug.
- Sexually active male participants must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 4 months after the last dose of study drug.
- Able to consume the prescribed meals.
- Adequate venous access for PK sampling.
Exclusion Criteria:
- Not recovered to grade ≤1 toxicity from previous anticancer treatments or previous investigational products (IPs); exception to this is alopecia or lymphopenia.
- Received IPs within 21 days or 5 half-lives of the first dosing day, whichever is shorter.
- Currently receiving other medications or radiation intended for the treatment of their malignancy. Hormonal therapy is allowed.
- Women of childbearing potential who are pregnant or breastfeeding.
- Taking a medication known to be a moderate or strong cytochrome P450 (CYP) 3A4 inhibitor or inducer or neurokinin-1 receptor antagonist (NK-1) inhibitor within 14 days prior to start of dosing.
- Taking a medication known to be a moderate or strong CYP2C8 inhibitor or inducer within 14 days prior to start of dosing.
- Taking an oral medication with a narrow therapeutic index known to be a P-glycoprotein (P-gp) substrate within 24 hours prior to start of dosing.
- Taking a medication known to be a P-gp inhibitor or inducer within 14 days prior to start of dosing in the study.
- Taking a medication known to be an organic anion transporting polypeptide 1B1/3 (OATP1B1/3) inhibitor.
- Require therapeutic use of warfarin. Participants receiving warfarin who are otherwise eligible and who may be appropriately managed with low molecular weight heparin, in the opinion of the investigator, may be enrolled provided they are switched to low molecular weight heparin at least 1 week before receiving study treatment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements.
- Major surgery to the upper gastrointestinal (GI) tract, or a history of GI disease or other medical condition that, in the opinion of the investigator may interfere with oral drug absorption.
- Cirrhosis of the liver or active hepatitis B or C. Enrollment of treated patients with hepatitis B or C are permitted, provided that (a) participant with chronic HBV is on anti-HBV prophylaxis, if needed based on the risk of reactivation (b) participants with HCV who had curative treatment are required to have a viral load that is below the level of quantification. A participant who is HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution should be eligible.
- Participants with known active HIV. Treated HIV participants who are on a stable antiretroviral treatment regimen for at least 4 weeks prior to enrollment, with a documented viral load < 400 copies/mL are permitted.
- History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity-type reaction to Cremophor.
- History of hypersensitivity to any of the excipients in encequidar tablets or oral paclitaxel.
- History of lactose intolerance.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: The Effect of Food on the Bioavailability of Oral Paclitaxel Administered with Encequidar
The Food Effect study (randomized 2-period, two-way crossover), participants will receive oPac+E in 2 sequences (fed/fasted or fasted/fed) in which encequidar is administered 1 hour before the oral paclitaxel capsules.
A treatment of oPac+E consisting of 3 daily doses will be administered on 3 consecutive days in each period 1 and 2. In Period 3, participants will receive concurrent administration of encequidar and oral paclitaxel after a low-fat meal.
|
Participant is either fasted or fed when taking Oral Paclitaxel in combination with Encequidar tablet
|
|
Eksperimentel: The Effect of Fasting on the Bioavailability of Oral Paclitaxel Administered with Encequidar
The Food Effect study (randomized 2-period, two-way crossover), participants will receive oPac+E in 2 sequences (fed/fasted or fasted/fed) in which encequidar is administered 1 hour before the oral paclitaxel capsules.
A treatment of oPac+E consisting of 3 daily doses will be administered on 3 consecutive days in each period 1 and 2. In Period 3, participants will receive concurrent administration of encequidar and oral paclitaxel after a low-fat meal.
|
Participant is either fasted or fed when taking Oral Paclitaxel in combination with Encequidar tablet
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Area under the plasma concentration-time curve (AUC) from 0 to time of last quantifiable concentration (AUC0-t) and AUC from time 0 to infinity (AUC0-INF) of oral paclitaxel when paclitaxel is administered one hour following encequidar.
Tidsramme: Plasma sample collected from pre-dose on Day 1 to Day 8.
|
The bioavailability of oral paclitaxel, measured by AUC0-t and AUC0-INF, will be determined after oral paclitaxel is administered one hour following encequidar dosing under both fed and fasting conditions.
AUC0-t will be calculated using trapezoidal rule.
AUC0-INF will be calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.
|
Plasma sample collected from pre-dose on Day 1 to Day 8.
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of participants with treatment emergent adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Tidsramme: From screening to the final follow-up visit.
|
Safety and tolerability will be evaluated in terms of treatment emergent AEs and serious adverse events.
This includes the types, incidence and severity of treatment emergent adverse events, as well as clinically significant abnormal laboratory test results, abnormal physical examination findings, abnormal vital signs, and abnormal electrocardiogram QT interval that emerge after treatment.
Clinical and laboratory adverse events will be primarily graded using NCI CTCAE Version 5.0.
|
From screening to the final follow-up visit.
|
|
Maximum observed concentration (Cmax) of oral paclitaxel when paclitaxel is administered one hour following encequidar.
Tidsramme: Plasma sample collected from pre-dose on Day 1 to Day 8.
|
The bioavailability of oral paclitaxel, measured by Cmax, will be determined after oral paclitaxel is administered one hour following encequidar dosing under both fed and fasting conditions.
|
Plasma sample collected from pre-dose on Day 1 to Day 8.
|
Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
AUC0-t and AUC0-INF for oral paclitaxel when administered concomitantly with encequidar
Tidsramme: Plasma sample collected from predose on Day 1 to Day 8.
|
The bioavailability of oral paclitaxel, measured by AUC0-t and AUC0-INF, will be determined after oral paclitaxel and encequidar are administered concomitantly under fed conditions.
AUC0-t will be calculated using trapezoidal rule.
AUC 0-INF will be calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.
|
Plasma sample collected from predose on Day 1 to Day 8.
|
Samarbejdspartnere og efterforskere
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- HHP-ORAX-100
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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