A Randomised, Open-label, Phase I Study to Determine the Effect of Food on the Pharmacokinetics of AZD1775 After Oral Dosing of a Capsule Formulation in Patients With Advanced Solid Tumours
Overview
- Phase
- Phase 1
- Intervention
- Treatment A - AZD1775 administered under fasted conditions
- Conditions
- Solid Tumours
- Sponsor
- AstraZeneca
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Cmax: maximum plasma drug concentration for AZD1775
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to assess the effect of food on the pharmacokinetics (PK) of a single dose of AZD1775 (printed capsules) in patients with advanced solid tumours.
Detailed Description
This is a Phase I, open-label, randomised, 2-period crossover design study in patients with advanced solid tumours. The purpose of this study is to assess the effect of food on the pharmacokinetics (PK) of a single dose of AZD1775 (printed capsules).In addition single dose safety and tolerability data will be gathered. Patients will be screened within 28 days of Day 1 of the first treatment period (Period 1). Patients will take part in 2 randomised treatment sequences each separated by a washout period of at least 5 and no more than 14 days. During Period 1, prior to administration of the first dose of study treatment, each patient will be randomised to 1 of 2 treatment sequences (Fasted-Fed or Fed-Fasted) to receive a single oral dose of 300 mg AZD1775 in each of the 2 treatment periods as follows: * Fasted (Treatment A): Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules). * Fed (Treatment B): Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules). Pharmacokinetic and safety assessments will be obtained for up to 72 hours post-dose in each treatment period. On completion of the study (ie, after collection of 72-hour PK sample and safety in period 2) patients will be evaluated per current assessments for their eligibility and interest to enrol into the open-label continued treatment access study (D6014C000007).
Investigators
Eligibility Criteria
Inclusion Criteria
- •For inclusion in the study patients should fulfil the following criteria:
- •Read and understand the informed consent form (ICF) and given written informed consent prior to any study procedures.
- •Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
- •Any prior palliative radiation must have been completed at least 7 days prior to the start of study treatment, and patients must have recovered from any acute adverse effects prior to the start of study treatment.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to
- •Baseline laboratory values within 7 days of study treatment initiation:
- •Absolute neutrophil count (ANC) ≥1500/μL.
- •Haemoglobin ≥9 g/dL.
- •Platelets ≥100,000/μL.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) or ≤5 x ULN if known hepatic metastases.
Exclusion Criteria
- •Patients should not enter the study if any of the following exclusion criteria are fulfilled:
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or personnel at the study centre).
- •Previous enrolment or randomisation and received study treatment in the present study. Patients can, however, be re-screened if the reason for the screen failure no longer exists.
- •Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or haemorrhage for at least 2 weeks after treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.
- •Use of any anti-cancer treatment drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first administration of AZD
- •For drugs for which 5 half lives is ≤21 days, a minimum of 10 days between termination of the prior treatment and administration of AZD1775 treatment is required.
- •No other anticancer-therapy (chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy \[except for palliative local radiotherapy\]), biological therapy or other novel agent is to be permitted while patient is receiving study treatment. Patients on LHRH analogue treatment for more than 6 months are allowed entry into the study and may continue at the discretion of the Investigator.
- •Patients suffering from conditions which are likely to adversely affect gastrointestinal motility and/or transit (for example, diarrhoea, vomiting or nausea, gastroparesis, irritable bowel syndrome and malabsorption) or patients with gastrointestinal resection (eg, partial or total gastrectomy) likely to interfere with absorption of study treatment.
- •Major surgical procedures ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days. No waiting period required following port-a-cath placement or other central venous access placement.
- •Grade \>1 toxicities from prior therapy, according to the Common Terminology Criteria for Adverse Events (CTCAE), excluding alopecia or anorexia.
Arms & Interventions
Treatment sequence 1 (Fasted-Fed)
To assess the PK of AZD1775 following oral dosing of the capsule formulation in patients with advanced solid tumours in either a fed or fasted condition.
Intervention: Treatment A - AZD1775 administered under fasted conditions
Treatment sequence 1 (Fasted-Fed)
To assess the PK of AZD1775 following oral dosing of the capsule formulation in patients with advanced solid tumours in either a fed or fasted condition.
Intervention: Treatment B - AZD1775 administered under fed conditions.
Treatment sequence 2 (Fed-Fasted)
To assess the PK of AZD1775 following oral dosing of the capsule formulation in patients with advanced solid tumours in either a fed or fasted condition.
Intervention: Treatment A - AZD1775 administered under fasted conditions
Treatment sequence 2 (Fed-Fasted)
To assess the PK of AZD1775 following oral dosing of the capsule formulation in patients with advanced solid tumours in either a fed or fasted condition.
Intervention: Treatment B - AZD1775 administered under fed conditions.
Outcomes
Primary Outcomes
Cmax: maximum plasma drug concentration for AZD1775
Time Frame: Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose
To investigate the effect of food on the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours
Area under the plasma concentration-time curve from zero to infinity for AZD1775
Time Frame: Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose
To investigate the effect of food on the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours
Area under the plasma concentration-time curve from time zero to the time "t" (AUC0-t) of the last quantifiable concentration for AZD1775
Time Frame: Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose
To investigate the effect of food on the PK of a single dose of AZD1775 printed capsules following oral dosing in patients with advanced solid tumours
Secondary Outcomes
- λz: Elimination rate constant for AZD1775(Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose)
- t½,: terminal half-life for AZD1775(Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose)
- Blood Pressure (mm Hg)(Until 30 days following the final dose of AZD1775)
- Apparent volume of distribution for AZD1775(Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose)
- Adverse Events, graded by the National Cancer Institute Common Terminology Criteria for Adverse Event's (CTCAE v4.3)(Until 30 days following the final dose of AZD1775)
- Apparent clearance following oral administration for AZD1775(Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose)
- Electrocardiogram (ECG) - A 12-lead safety ECG (paper ECG printout of 10 seconds for Investigator review)(Until 7 days following the final dose of AZD1775)
- Evaluation of Clinical Chemistry Parameters (Albumin, Alanine Transaminase, Aspartate Transaminase, Alkaline Phosphatase, Bilirubin, Calcium, Creatinine, Glucose, Total protein, Chloride, Potassium, Sodium, Urea nitrogen)(Until 30 days following the final dose of AZD1775)
- tmax,: time to reach maximum plasma concentration for AZD1775(Blood samples are collected on Day 1 of each treatment period at pre-dose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours post AZD1775 dose)
- Pulse Rate (beats/min)(Until 30 days following the final dose of AZD1775)
- Body Temperature (°C)(Until 30 days following the final dose of AZD1775)
- Complete physical examination including performance status assessed using the Eastern Cooperative Oncology Group (ECOG) Performance Status criteria.(Until 30 days following the final dose of AZD1775)
- Evaluation of Haematology Parameters (Haemoglobin, Leukocyte and Leukocyte counts, Red blood cell count, Haematocrit and Platelet Count)(Until 30 days following the final dose of AZD1775)