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

NCT01895946 | Completed Phase 1 Results

• 1 other identifier: D3610C00007
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

Advanced Solid Malignancy,; Safety and Tolerability,; Pharmacokinetics, Pharmacodynamics,; Tumour Response,

Keywords

Advanced solid malignancy, AZD5363,; food effect,; formulation comparison

Outcome Measures

Primary Outcomes (2)

• Ratio of Css,Max for Day 4 to Day 11

  The actual sampling times were used in the pharmacokinetics (PK) parameter calculations and PK parameters were derived using standard non-compartmental methods. Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined: Maximum plasma concentration at steady state (Css max), time to Css,max (tss max), minimum plasma concentration at steady state (Css min), area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and apparent clearance (CLss/F). Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss. Ratio of Css,max for Day 4 to Day 11 have been derived.

  Day 4 and Day 11

• Ratio of AUCss for Day 4 to Day 11

  The actual sampling times were used in the parameter calculations and PK parameters were derived using standard non-compartmental methods. Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined: Css max, tss max, Css min, area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and CLss/F. Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss. Ratio of AUCss for Day 4 to Day 11 have been derived.

  Day 4 and Day 11

Secondary Outcomes (5)

• Efficacy: Best Objective Response (BOR)

  Assessed every 6 weeks, up to 36 weeks

• Efficacy: Disease Control at Week 12

  Week 12

• Efficacy: Target Lesion Size, Percentage Change From Baseline at Week 12

  Week 12

• Efficacy: Target Lesion Size, Best Percentage Change From Baseline

  Assessed every 6 weeks up to 36 weeks

• Efficacy: Progression-free Survival (PFS)

  Assessed every 6 weeks up to 36 weeks

Study Arms (2)

Part A: Formulation Switch

EXPERIMENTAL

AZD5363 tablet twice daily followed by AZD5363 capsule twice daily on an intermittent regimen (4 days on, 3 days off).

Drug: AZD5363

Part B: Food effect

EXPERIMENTAL

AZD5363 tablet twice daily on an intermittent regimen (4 days on, 3 days off) with/without food on one occasion

Drug: AZD5363

Interventions

AZD5363 DRUG

Oral AZD5363 twice daily, 4 days on 3 days off: tablet formulation for one week, followed by two weeks with capsule formulation.

Part A: Formulation Switch

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Computerised Tomography (CT), Magnetic Resonance Imaging (MRI) or plain X-ray and is suitable for repeated assessment
• Estimated life expectancy of more than 12 weeks

You may not qualify if:

• 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 Human Immunodeficiency Virus (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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (3)

Research Site

Amsterdam, 1066 CX, Netherlands

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Research Site

Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Interventions

capivasertib

Limitations and Caveats

Small numbers of patients in the first (fasted) and second (fed) treatment periods overall make interpretation difficult.

Results Point of Contact

• Title: Dr Justin P. O. Lindemann, MBChB MBA, Medical Science Director, AZD5363
• Organization: AstraZeneca UK Limited

Justin.Lindemann@astrazeneca.com

(0)7920 250301

Study Officials

• Justin Lindemann, MSD

  AstraZeneca

  STUDY DIRECTOR

• Udai Banerji, MD, PhD

  Institute of Cancer Research, United Kingdom

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: June 21, 2013
• First Posted: July 11, 2013
• Study Start: December 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: July 1, 2015
• Last Updated: May 25, 2016
• Results First Posted: May 25, 2016

Record last verified: 2016-04

Locations

GB (2); NL (1)