The Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol

Study Overview
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Brief Summary
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This is multicenter, open-label, 2-part crossover study. Eligible subjects will have metastatic or unresectable solid tumors. This study includes a pretreatment and treatment phase. The pretreatment phase consists of screening and baseline. The treatment phase consists of Periods 1 and 2 (Part A), Treatment (Part B), and Follow-up.

Official Title
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An Open-label, Crossover Study of the Effect of Food on the Pharmacokinetics of Paclitaxel Administered Orally as Oraxol

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: Oraxol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent 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. Measurable disease as per RECIST v1.1 criteria Adequate hematologic status Adequate liver function. Adequate renal function Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Life expectancy of at least 3 months. Women must be postmenopausal or surgically sterile. Sexually active male subjects must use a barrier method of contraception during the study. Able to consume the prescribed meals Exclusion Criteria: Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous investigational products (IPs). Received IPs within 21 days or 5 half-lives of the first dosing day, whichever is shorter Are 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. Currently taking a concomitant medication, other than a premedication, that is: A strong P-glycoprotein (P-gp) inhibitor or inducer. An oral medication with a narrow therapeutic index known to be a P-gp substrate. Medications known to be strong inhibitors or inducers of cytochrome P450 (CYP) 2C8 or medications known to be strong CYP3A4 inhibitors or inducers. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or any concomitant illness that would limit compliance with study requirements. Major surgery to the upper gastrointestinal (GI) tract, or have a history of GI disease that may interfere with oral drug absorption. Cirrhosis of the liver or known active hepatitis B, hepatitis C, or HIV History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity-type reaction to Cremophor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This will be an open-label, 2-part, crossover study to assess the effect of food on Oraxol exposure. The study will consist of the following periods: Screening, Baseline, Periods 1 and 2 (Part A), Treatment (Part B), and Follow-up. Part A will assess the effect of food on Oraxol pharmacokinetics. In Part A, subjects will be randomized to the sequence (fed/fasted or fasted/fed conditions) under which they will be administered single-dose treatment after an overnight fast. There will be a minimum of 7 days after Period 1 treatment before subjects cross over to Period 2 treatment. Subjects who have participated in the PK assessments in Part A of the study may continue into Part B, during which Oraxol will be dosed for 3 consecutive days per week under fasting conditions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fed/ Fasted Treatment Sequence<br>Subjects will be assigned a fed/fasted sequence. Fed sequence- subjects will fast overnight and continue fasting until they consume a standardized test meal at a predetermined time after paclitaxel administration. Fasted Sequence- subjects will fast overnight and continue fasting until 4 hours post paclitaxel dose. | Drug: Oraxol<br>* Oraxol will be supplied as paclitaxel capsules and HM30181AK-US tablets.<br>* Other names: Paclitaxel and HM30181AK-US;|
| Active Comparator: Fasted/ Fed Treatment Sequence<br>Subjects will be assigned a fasted/fed sequence. Fasted Sequence- subjects will fast overnight and continue fasting until 4 hours post paclitaxel dose. Fed sequence- subjects will fast overnight and continue fasting until they consume a standardized test meal at a predetermined time after paclitaxel administration. | Drug: Oraxol<br>* Oraxol will be supplied as paclitaxel capsules and HM30181AK-US tablets.<br>* Other names: Paclitaxel and HM30181AK-US;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the concentration-time profile of Oral Paclitaxel in plasma for 168 hours when taken with or without food. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the concentration-time profile of HM30181 in plasma for 168 hours when taken with or without food. |  | 24 months | 
| The proportion of patients with tumor responses after the initiation of treatment. | RECIST v1.1 criteria defined as complete response, partial response, stable disease or progressive disease | At baseline and every 8 weeks through study completion, approximately 24 months | 
| Incidence of Adverse Events (Safety and Tolerability) | Evaluate the safety of Oraxol. Number of participants with treatment-related adverse events. | 24 months |