Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability

Safety and Tolerability, Clinical Trial

— OAK  

Official title:

A Phase I, Open-Label, Multicentre Study to Compare Two Dosage Formulations of AZD5363 and to Establish the Effect of Food on the Pharmacokinetic Exposure, Safety and Tolerability of AZD5363 in Patients With Advanced Solid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01895946
• Other study ID #: D3610C00007
• Status: Completed
• Phase: Phase 1
• First received: June 21, 2013
• Last updated: July 30, 2015
• Start date: December 2013
• Est. completion date: July 2015

Study information

• Verified date: July 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability

Description:

This study is designed to investigate the safety, tolerability and pharmacokinetics of a new drug, AZD5363, in patients with advanced cancer . This study will investigate how the body handles AZD5363 (ie, how quickly the body absorbs and removes the drug), the comparison of a capsule and a tablet formulation and the effect of food on AZD5363 tablet formulation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: July 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Aged at least 18 years. -The presence of a solid, malignant tumour, excluding lymphoma, that is resistance to standard therapies or for which no standard therapies exist. - The presence of at least one lesion that can be accurately assessed at baseline by CT, MRI or plain X-ray and is suitable for repeated assessment. - Estimated life expectancy of more than 12 weeks

Exclusion Criteria:

• Clinically significant abnormalities of glucose metabolism. - Spinal cord compression or brain metastases unless asymptomatic, treated and stable (not requiring steroids).
• Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV. - Evidence of clinically significant cardiac abnormalities, uncontrolled hypotension, left ventricular ejection fraction below the lower limit of normal for the site or experience of significant cardiac interventional procedures. - A bad reaction to AZD5363 or any drugs similar to it in structure or class.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Malignancy,
• Neoplasms
• Pharmacokinetics, Pharmacodynamics,
• Safety and Tolerability,
• Tumour Response,

Intervention

Drug:
• AZD5363
Oral AZD5363 twice daily, 4 days on 3 days off: tablet formulation for one week, followed by two weeks with capsule formulation.
• AZD5363
Oral AZD5363 twice daily, 4 days on 3 days off, tablet formulation. On day 4 AZD5363 tablet without food. On day 11 AZD5363 tablet with food.

Locations

Country	Name	City	State
Netherlands	Research Site	Amsterdam
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: AZD5363 PK (plasma concentration) of tablet and capsule formulations		Up to Day 11	No
Primary	Part B: PK (plasma concentration) of a AZD5363 tablet formulation with food		Up to Day 11	No
Secondary	Part A: PK for AZD5363 new tablet formulation (maximum plasma concentration at steady state)		Up to Day 11	No
Secondary	Part B: Within-patient comparison of steady state exposure of AZD5363 tablet with/without food (plasma concentrations Css max and Css min)		Up to Day 11	No
Secondary	Part A and B: Safety and tolerability of AZD5363 in terms of adverse events		Screening to 28 days after study drug discontinuation	Yes
Secondary	Parts A,B: Obtaining of a preliminary assessment of anti-tumour activity of AZD5363 via use of Response Evaluation Criteria in Sold Tumours (RECIST) version		6 weekly intervals until discontinuation of study therapy	No
Secondary	Part B: Safety and tolerability of AZD5363 tablet in terms of adverse events and serious adverse events, death, changes from baseline of laboratory data (clinical chemistry, haematology, urinalysis), vital signs, and electrocardiogram (ECG) parameters		Screening to 28 days after study drug discontinuation	Yes
Secondary	Part A: PK for AZD5363 new tablet formulation (time to Cmax)		Up to Day 11	No
Secondary	Part A: PK for AZD5363 new tablet formulation (area under plasma concentration time curve at steady state)		Up to Day 11	No
Secondary	Part A: PK for AZD5363 new tablet formulation (oral plasma clearance at steady state)		Up to Day 11	No
Secondary	Part B: Within-patient comparison of steady state exposure of AZD5363 tablet with/ without food (time to Css max)		Up to Day 11	No
Secondary	Part B: Within-patient comparison of steady state exposure of AZD5363 tablet with/without food (area under the plasma concentration-time curve at steady state)		Up to Day 11	No
Secondary	Part A and B: Safety and tolerability of AZD5363 in terms of death		Screening to 28 days after study drug discontinuation	Yes
Secondary	Part A and B: Safety and tolerability of AZD5363 in terms of changes from baseline of laboratory data		Screening to 28 days after study drug discontinuation	Yes
Secondary	Part A and B: Safety and tolerability of AZD5363 in terms of changes in electrocardiogram (ECG) parameters		Screening to 28 days after study drug discontinuation	Yes