Bioavailability of AZD0284 and IV Microtracer Study

NCT03029741 | Completed Phase 1

• 2 other identifiers: D7800C000022016-004260-19
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The Sponsor is developing the study drug, AZD0284, for the potential treatment of Plaque psoriasis. Psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery scales. It occurs when skin cells are replaced more quickly than usual. The seriousness of psoriasis varies greatly from person to person. For some people it is a minor irritation, but for others it can have a major impact on their quality of life. . The purpose of the study is to determine how much of AZD0284 is taken up by the body. The safety and tolerability of the drug will also be assessed. It is hoped that the study drug will improve the management of psoriasis.

Conditions

Plaque Psoriasis Vulgaris

Outcome Measures

Primary Outcomes (23)

• Determination of absolute bioavailability of AZD0284

  Absolute bioavailability of AZD0284 will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD0284 / AUC of the IV dose of \[14C\]AZD x IV dose/Oral dose x 100

  PK blood samples: pre-dose, post oral dosing at hour, 0.5, 1, 2, 0, 0.5, 1, 2, 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5,3.75, 4, 5, 6, 7, 8, 9, 11, 12, 15, 24, 27, 36, 48 and 72.

• Cmax for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0824 in terms of the maximum observed plasma concentration (Cmax) for \[14C\]AZD0284

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• Tmax for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the the time to maximum observed plasma concentration (Tmax) for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• AUC(0-last) for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the area under the concentration-time curve from dosing to the last measurable concentration for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• AUC(0-inf) for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms the area under the concentration-time curve from dosing extrapolated to infinity for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• AUC%extrap for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the percentage of AUC(0-inf) extrapolated beyond the last measured for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• lambda-z for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the terminal elimination rate constant calculated from the slope of the apparent elimination phase for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• T1/2 for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the apparent terminal elimination half-life for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• CL (total clearance) for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the terminal elimination rate constant calculated from the slope of the apparent elimination phase for \[14C\]AZD0284

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• Vz for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the volume of distribution at steady state for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• Vss for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the volume of distribution at steady state for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• MRT (mean residence time) for [14C]AZD0284

  Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the mean residence time for \[14C\]AZD0284.

  PK blood samples:pre-dose, time relative to oral dosing at hour: 2.83, 2.92, 2.92, 3, 3.08, 3.17, 3.33, 3.5, 3.75, 4, 5, 6, 7, 8, 9, 11, 15, 27, 36, 48 and 72.

• Cmax for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0824 in terms of the maximum observed plasma concentration (Cmax) for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• Tmax for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the the time to maximum observed plasma concentration (Tmax) for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• Tlag for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• AUC (0-last) for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the area under the concentration-time curve from dosing to the last measurable concentration for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• AUC(0-inf) for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms the area under the concentration-time curve from dosing extrapolated to infinity for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• AUC%extrap for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the percentage of AUC(0-inf) extrapolated beyond the last measured time point for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• lambda-z for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the terminal elimination rate constant calculated from the slope of the apparent elimination phase for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• T1/2 for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the apparent terminal elimination half-life for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

• CL/F for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the apparent total clearance for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 36, 48 and 72.

• Vz/F for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the apparent volume of distribution for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 , 36, 48 and 72.

• MRT for AZD0284

  Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms the mean residence time for AZD0284.

  PK blood samples: pre-dose, time relative to oral dosing at hour, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72.

Secondary Outcomes (5)

• To collect further information about the safety and tolerability of AZD0284 by assessing physical examinations.

  Targeted physical examination:screening, pre-dose, time relative to oral dosing at hour 72.

• To collect further information about the safety and tolerability of AZD0284 by assessing telemetry

  Continuous ECG monitoring will commence approximately 10 minutes before dosing commences until 24 hours after the oral dose.

• To collect further information about the safety and tolerability of AZD0284 by assessing safety laboratory tests

  Haematology and clinical chemistry:screening, pre-dose, time relative to oral dosing at hour 24 and 72, virology at screening.

• To collect further information about the safety and tolerability of AZD0284 by assessing vital signs

  Blood pressure and pulse rate: screening, pre-dose, post oral dosing at hour 1, 2, 3, 4, 6, 8, 12, 24 and 72.

• To collect further information about the safety and tolerability of AZD0284 by assessing 12 Lead Electrocardiogram (ECG)

  ECGs: screening, pre-dose, post oral dosing at hour, 1, 2, 3, 4, 6, 8, 12, 24 and follow up.

Study Arms (1)

Bioavailability of AZD0284

EXPERIMENTAL

To assess the absolute bioavailability of a single oral dose of AZD0284 in healthy subjects. To assess the pharmacokinetics (PK) of a single intravenous (IV) microdose of \[14C\]AZD0284 in healthy subjects.

Drug: AZD0284; Drug: [14C]AZD0284

Interventions

AZD0284 DRUG

Subjects will receive a single oral dose of 4 to 120 mg AZD0284 oral suspension 5 mg/mL in the fasted state

Bioavailability of AZD0284

[14C]AZD0284 DRUG

Following administration of the AZD0284 oral suspension subjects will receive an IV infusion of 20 μg \[14C\]AZD0284 solution

Bioavailability of AZD0284

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated, written informed
• Healthy males or non-pregnant, non-lactating healthy females.
• Age 18 to 65 years of age.
• Suitable veins for cannulation or repeated venepuncture.
• Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
• Post-menopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Body mass index of 18.0 to 30.0 kg/m2, inclusive, or, if outside the range, considered not clinically significant by the investigator, and weigh at least 50 kg and no more than 100 kg, inclusive.
• Must be willing and able to communicate and participate in the whole study.
• Must agree to use an adequate method of contraception

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results of the volunteer's ability to participate in the study.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• Subject who have increased risk of infection History and/or presence of tuberculosis (TB) positive result for IFN-y release assay (IGRA) (ie QuantiFERON TB-Gold). The test may be repeated if the initial test result is indeterminate.
• Is in a high-risk group for human immunodeficiency virus (HIV) infection within the last 6 months.
• Subjects with a disease history suggesting abnormal immune function in the judgement of the investigator. (This does not include mild allergy such as childhood asthma or eczema).
• Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis, as judged by the investigator.
• Any clinically significant abnormal findings in vital signs, as judged by the investigator.
• Any clinically significant abnormal findings in 12-lead ECG, as judged by the investigator.
• Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or HIV results.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Nottingham, United Kingdom

Location

MeSH Terms

Interventions

AZD-0284

Study Officials

• Philip Evans, MBChB, MRCS

  Quotient Clinical Ltd, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: February 21, 2017
• Primary Completion: March 23, 2017
• Study Completion: March 23, 2017
• Last Updated: April 13, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)