AZD4635 Relative Bioavailability Study

NCT03710434 | Completed Phase 1

• 2 other identifiers: D8730C000022018-003366-14
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the pharmacokinetics and relative bioavailability of AZD4635 solid oral formulation and compare with the nano-suspension reference formulation with the option to assess food effect, pH effect and absolute bioavailability

Conditions

Healthy Volunteers

Keywords

Phase 1, healthy, bioavailability, pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Maximum observed plasma concentration (Cmax) of AZD4635 solid oral formulation and nano-suspension (reference)

  Assessment of maximum concentration (Cmax) in plasma

  Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h

• Exposure to AZD4635 solid oral formulation and nano-suspension (reference)

  Assessment of exposure through measurement of area under the curve (AUC) in plasma

  Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h

Secondary Outcomes (17)

• Time to maximum concentration (tmax) of AZD4635 solid oral formulation variants 1 and 2 in plasma

  Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h

• Maximum concentration (Cmax) of AZD4635 solid oral formulation variants 1 and 2 in plasma

  Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h

• Area under the plasma concentration-time curve from zero to time of last measurable concentration (AUClast) for AZD4635 solid oral formulation variants 1 and 2

  Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h

• Area under the plasma concentration-time curve from zero to 48 hours (AUC 0-48) for AZD4635 solid oral formulation variants 1 and 2

  Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h and 48h

• Area under the plasma concentration-time curve from zero to infinity (AUC 0-inf.) for AZD4635 solid oral formulation variants 1 and 2

  Blood samples collected pre-dose, and postdose at 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h, 96h and 120h

Study Arms (8)

Part A - nano-suspension

EXPERIMENTAL

Subjects will receive single dose of AZD4635 50mg nano-suspension (reference) in the fasted state.

Drug: AZD4635 50 mg nano-suspension (reference)

Part A - solid oral formulation

EXPERIMENTAL

Subjects will receive single dose of AZD4635 50mg solid oral formulation, in the fasted state.

Drug: AZD4635 solid oral formulation - fasted

Part B-solid oral formulation with food

EXPERIMENTAL

Subjects will receive a single dose AZD4635 solid oral formulation after high fat meal.

Drug: AZD4635 solid oral formulation - fed

Part B - solid oral formulation with PPI

EXPERIMENTAL

Subjects will receive 30 mg lansoprazole BID and a single dose of AZD4635 solid oral formulation in the fasted state.

Drug: Lansoprazole and AZD4635 50 mg solid oral formulation

Part B - dose exploration 1

EXPERIMENTAL

If dose adjustment is required, subjects will receive a different single dose (XX mg) of AZD4635 solid oral formulation, in the fasted state.

Drug: AZD4635 solid oral formulation - fasted

Part B - dose exploration 2

EXPERIMENTAL

If dose adjustment is required, subjects will receive a different single dose (YY mg) of AZD4635 solid oral formulation, in the fasted state.

Drug: AZD4635 solid oral formulation - fasted

Part B - variant 1

EXPERIMENTAL

Subjects will receive a single dose of AZD4635 solid oral formulation, variant 1 in the fasted state and optional \[14C\] AZD4635 IV microtracer.

Drug: AZD4635 solid oral formulation variant 1 - fasted; Drug: [14C] AZD4635 IV microtracer - fasted

Part B - variant 2

EXPERIMENTAL

Subjects will receive a single dose of AZD4635 solid oral formulation, variant 2 in the fasted state.

Drug: AZD4635 solid oral formulation variant 2 - fasted

Interventions

AZD4635 50 mg nano-suspension (reference) DRUG

Subjects will receive a single dose of AZD4635 50 mg nano-suspension (reference) in the fasted state.

Part A - nano-suspension

AZD4635 solid oral formulation - fasted DRUG

Subjects will receive a single dose of AZD4635 solid oral formulation, in the fasted state.

Part A - solid oral formulation; Part B - dose exploration 1; Part B - dose exploration 2

AZD4635 solid oral formulation - fed DRUG

Subjects will receive a single dose of AZD4635 solid oral formulation, in the fed state.

Part B-solid oral formulation with food

Lansoprazole and AZD4635 50 mg solid oral formulation DRUG

Subjects will receive lansoprazole 30 mg BID for 5 days followed by a single dose of AZD4635 50 mg solid oral formulation in the fasted state.

Part B - solid oral formulation with PPI

AZD4635 solid oral formulation variant 1 - fasted DRUG

Subjects will receive a single dose of AZD4635 solid oral formulation, variant 1 in the fasted state.

Part B - variant 1

AZD4635 solid oral formulation variant 2 - fasted DRUG

Subjects will receive a single dose of AZD4635 solid oral formulation, variant 2 in the fasted state.

Part B - variant 2

[14C] AZD4635 IV microtracer - fasted DRUG

Subjects will receive a single dose of \[14C\] AZD4635 IV microtracer. This intervention will be co-administered with AZD4635 solid oral formulation variant 1.

Part B - variant 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male subjects aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture and IV infusion.
• Have a body mass index of 18.0 to 32.0 kg/m2, and weigh at least 50 kg and no more than 100 kg.
• Must be willing and able to communicate and participate in the whole study
• Must agree to adhere to the contraception requirements, as precaution should avoid fathering a child by either true abstinence or use together, with their female partner/spouse, a highly effective contraception form of birth control in combination with a barrier method, starting from the time of AZD4635 administration until 90 days after the last dose of AZD4635.

You may not qualify if:

• History of any clinically significant disease or disorder which in investigator opinion, may put volunteer at risk because of participation in the study, or influence results of 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.
• Presence of refractory nausea and vomiting or chronic gastrointestinal diseases.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any confirmed clinically significant abnormalities in clinical chemistry, haematology or urinalysis as judged by the investigator
• Any confirmed clinically significant abnormal findings in vital signs, as judged by investigator.
• BP \>140/90 mmHg or history of hypertension.
• Any confirmed clinically significant abnormal findings in 12-lead ECG, as judged by investigator.
• Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
• Known or suspected history of drug or alcohol abuse within the past 2 years, as judged by the investigator.
• Plasma donation within 1 month of screening or any blood donation/loss of more than 500 mL of blood during the 3 months prior to screening.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4635 or the formulation excipients. Hayfever is allowed unless it is active.
• Current smokers and those who have smoked within last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission.
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within last 12 months.
• Positive screen for drugs of abuse at screening or admission to the clinical unit or positive screen for alcohol at screening or admission to the clinical unit.

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

Related Links

• Results of this clinical trial are available on www.astrazenecaclinicaltrials.com

MeSH Terms

Interventions

Lansoprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sharan Sidhu, MBChB, BAO, MRCS, MFPM

  Quotient Sciences Limited (indemnified by Medical Protection Society)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: October 18, 2018
• Study Start: November 1, 2018
• Primary Completion: April 2, 2019
• Study Completion: April 2, 2019
• Last Updated: May 7, 2020

Record last verified: 2020-05

Locations

GB (1)