PET Study to Determine Muscarinic Receptor Occupancy in Lungs After Inhalation of AZD2115 and Tiotropium

NCT03097380 | Completed Phase 1

• 1 other identifier: D3060C00014
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label study using positionemissiontomography (PET) to explore the binding of AZD2115 and Tiotropium to muscarinic receptors in the lungs in healthy volunteers after inhalation.

Conditions

Healthy Volunteers

Keywords

Healthy volunteer study

Outcome Measures

Primary Outcomes (1)

• Reduction in distribution volume (VT)%

  To describe the AZD2115 dose-muscarinic receptor occupancy relationship in the lungs in healthy volunteers

  up to 9 h post dose

Secondary Outcomes (1)

• Receptor occupancy (RO) %

  up to 9 h post dose

Study Arms (3)

AZD2115

EXPERIMENTAL

Drug: AZD2115; Radiation: [11C]AZ13754366

Spiriva (Tiotropium)

ACTIVE COMPARATOR

Drug: SPIRIVA; Radiation: [11C]AZ13754366

[11C]AZ13754366

EXPERIMENTAL

Radiation: [11C]AZ13754366

Interventions

AZD2115 DRUG

AZD2115

AZD2115

SPIRIVA DRUG

Tiotropium

Spiriva (Tiotropium)

[11C]AZ13754366 RADIATION

Radioligand

AZD2115; Spiriva (Tiotropium); [11C]AZ13754366

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: male
• 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 20 to 50 years (inclusive)
• Male subjects must be surgically sterile or use an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the first dose) and for 3 months after the last dose of study drug to prevent pregnancy in a partner
• Body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at least 50.0 kg and no more than 100.0 kg, inclusive
• Able and willing to participate in all scheduled evaluations and abide by all study restrictions
• Ability to inhale from the study drug training devices at visit 1
• Subjects who are blood donors should not donate blood during the study and for 3 months following their last dose of study drug.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the study results or the subject's ability to participate in the study.
• Any clinical significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP)
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator.
• Any positive results on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV)
• Abnormal vital signs, after 10 minutes of supine rest, defined as any of the following:
• Systolic blood pressure (BP) \<90 mmHg or \>140 mmHg
• Diastolic BP \<50 mmHg or \>90 mmHg
• Heart rate \<45 bpm or \> 100 bpm
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes, as determined by the investigator. This may include subjects with any of the following:
• PR (PQ) interval prolongation of clinical significance as judged by the Investigator
• Intermittent second or third degree AV block (AV block II Mobitz type 1 Wenchebach, while asleep or in deep rest is not disqualifying)
• Incomplete, full, or intermittent bundle branch block (QRS less than 110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
• Abnormal T wave morphology, particularly in the protocol-defined primary lead
• Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) greater than 450 ms or shortened QTcF less than 340 ms or a family history of long QT syndrome.
• History of alcohol abuse or excessive intake of alcohol, as judged by the investigator.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Stockholm, 171 76, Sweden

Location

Related Publications (2)

• Cselenyi Z, Jucaite A, Ewing P, Stenkrona P, Kristensson C, Johnstrom P, Schou M, Bolin M, Halldin C, Larsson B, Grime K, Eriksson UG, Farde L. Proof of lung muscarinic receptor occupancy by tiotropium: Translational Positron Emission Tomography studies in non-human primates and humans. Front Nucl Med. 2023 Jan 18;2:1080005. doi: 10.3389/fnume.2022.1080005. eCollection 2022.

  PMID: 39354985 DERIVED

• Cselenyi Z, Jucaite A, Kristensson C, Stenkrona P, Ewing P, Varrone A, Johnstrom P, Schou M, Vazquez-Romero A, Moein MM, Bolin M, Siikanen J, Gryback P, Larsson B, Halldin C, Grime K, Eriksson UG, Farde L. Quantification and reliability of [11C]VC - 002 binding to muscarinic acetylcholine receptors in the human lung - a test-retest PET study in control subjects. EJNMMI Res. 2020 Jun 3;10(1):59. doi: 10.1186/s13550-020-00634-0.

  PMID: 32495011 DERIVED

MeSH Terms

Interventions

Tiotropium Bromide

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Design

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

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 31, 2017
• Study Start: April 26, 2017
• Primary Completion: December 30, 2017
• Study Completion: December 30, 2017
• Last Updated: August 30, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)