Phase I Study to Assess the Effect of Food on AZD1775 Pharmacokinetics in Patients With Advanced Solid Tumours

NCT03315091 | Completed Phase 1 FDA Drug

• 1 other identifier: D6014C00005
• Study Type: interventional
• Target: 31
• Locations: 3 countries
• Sites: 7

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.

Conditions

Solid Tumours

Keywords

Pharmacokinetics, WEE1 inhibitor, food effect, safety assessments

Outcome Measures

Primary Outcomes (3)

• Area under the plasma concentration-time curve from zero to infinity for AZD1775

  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

  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

• Area under the plasma concentration-time curve from time zero to the time "t" (AUC0-t) of the last quantifiable concentration for AZD1775

  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

  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

• Cmax: maximum plasma drug concentration for AZD1775

  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

  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

Secondary Outcomes (13)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Treatment sequence 1 (Fasted-Fed)

EXPERIMENTAL

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.

Drug: Treatment A - AZD1775 administered under fasted conditions; Drug: Treatment B - AZD1775 administered under fed conditions.

Treatment sequence 2 (Fed-Fasted)

EXPERIMENTAL

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.

Drug: Treatment A - AZD1775 administered under fasted conditions; Drug: Treatment B - AZD1775 administered under fed conditions.

Interventions

Treatment A - AZD1775 administered under fasted conditions DRUG

Premedication with Kytril (granisetron) 1 mg intravenously or Zofran (ondansetron) 8 mg intravenously within 30 to 40 minutes prior to administration of the AZD1775 capsules. Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules) administered orally under fasted conditions. The drug class of AZD1775 is Wee-1 kinase inhibitor.

Treatment sequence 1 (Fasted-Fed); Treatment sequence 2 (Fed-Fasted)

Treatment B - AZD1775 administered under fed conditions. DRUG

Premedication with Kytril (granisetron) 1 mg intravenously or Zofran (ondansetron) 8 mg intravenously within 30 to 40 minutes prior to administration of the AZD1775 capsules. Single dose 300 mg AZD1775, (3 x 100 mg, printed capsules) administered orally under fed conditions. The drug class of AZD1775 is Wee-1 kinase inhibitor.

Treatment sequence 1 (Fasted-Fed); Treatment sequence 2 (Fed-Fasted)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.
• 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.
• Serum bilirubin within normal limits (WNL) or ≤1.5 x ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
• Serum creatinine ≤1.5 x ULN, or measured creatinine clearance (CrCl) calculated by Cockcroft-Gault method ≥45 mL/min (confirmation of creatinine clearance is only required when creatinine is \>1.5 x ULN) CrCl (glomerular filtration rate) = (140-age) x (weight/kg) x Fa (72 x serum creatinine mg/dL)
• where F = 0.85 for females and F = 1 for males
• Female patients who are not of childbearing potential and fertile females of childbearing potential who agree to use adequate contraceptive measures that are in during screening (or consent), for the duration of the study, and for 1 month after treatment stops, and who are not breastfeeding, and who have a negative serum or urine pregnancy test prior to the start of study treatment.
• Male patients should be willing to use barrier contraception (ie, condoms) for the duration of the study and for 3 months after study treatment discontinuation
• Female or male patients ≥18 years.

You may not qualify if:

• 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 AZD1775. 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.
• Patient has an inability to swallow oral medications. Note: Patient may not have a percutaneous endoscopic gastrostomy tube or be receiving total parenteral nutrition.
• Patients who are not non-smokers or light smokers (no more than 5 cigarettes per day) and who cannot abstain from smoking from 2 weeks prior to the first administration of AZD1775 until after the last PK sample collection in Period 2.
• Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of AZD1775.
• Patient has had prescription or non-prescription drugs or other products known to be sensitive to cytochrome P450 (CYP)3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last administration of AZD1775. Co administration of aprepitant or fosaprepitant during this study is prohibited
• Patient has had adjustments to prescription or non-prescription drugs or other products known to be weak inhibitors and/or inducers of CYP3A4 within 1 week prior to the first administration of AZD1775.
• Herbal preparations taken within 7 days of study entry. However, in the case of St John's wort, patients cannot have taken this herbal preparation 21 days prior to first administration of AZD1775.
• Patients who have taken any proton pump inhibitors (omeprazole, lansoprazole, esomeprazole, pantoprazole, etc) within 7 days of first administration of AZD1775.

Sponsors & Collaborators

• AstraZeneca: lead
• Quintiles, Inc.: collaborator

Study Sites (7)

Research Site

Bordeaux, 33075, France

Location

Research Site

Saint-Herblain, 44805, France

Location

Research Site

Amsterdam, 1066 CX, Netherlands

Location

Research Site

Amsterdam, 1081 HV, Netherlands

Location

Research Site

Maastricht, 6229 HX, Netherlands

Location

Research Site

Glasgow, G12 0YN, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Study Officials

• Lone Ottesen, MD

  AstraZeneca

  STUDY DIRECTOR

• Henk Verheul, MD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 19, 2017
• Study Start: September 29, 2017
• Primary Completion: April 5, 2018
• Study Completion: April 5, 2018
• Last Updated: April 30, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); GB (2); FR (2)