Evaluation of Histamine H3 Receptor Radioligand [11C]AZ12807110 and Histamine H3 Receptor Occupancy of AZD5213 After Oral Administration

NCT01194986 | Completed Phase 1

• 2 other identifiers: D3030C000032009-010702-11
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate features of radioligand \[11C\]AZ12807110 and how much AZD5213 displaces radioligand from histamine receptors when given together.

Conditions

Brain Distribution of [11C]AZ12807110 and AZD5213

Keywords

Receptor binding; Histamine H3 receptor; binding; radioligand

Outcome Measures

Primary Outcomes (2)

• Distribution volume (VT)

  Venous blood samples for determination of concentrations of AZD5213 in plasma will be taken on many occasions from pre-dose until 48 h post-dose. Single PET measurement will take maximum 2 hours.

• Estimation of the plasma concentration resulting in 50% receptor occupancy (Ki, pl).

  Each healthy volunteer in the main panel will complete 3 PET measurements using radioligand; one at baseline and 2 after treatment with AZD5213.

  Venous blood samples for determination of concentrations of AZD5213 in plasma will be taken on many occasions from pre-dose until 48 h post-dose.

Secondary Outcomes (2)

• Adverse events

  Collected from Day 1 to follow-up

• Vital signs (body temperature, BP and pulse)

  Measured at screening, study days -1 to day 3 and at follow-up

Study Arms (2)

Pilot panel

EXPERIMENTAL

\[11C\]AZ12807110 distribution and kinetics

Other: [11C]AZ12807110

Main panel

EXPERIMENTAL

Histamine receptor occupancy reached by AZD5213

Other: [11C]AZ12807110; Drug: AZD5213

Interventions

[11C]AZ12807110 OTHER

Radioligand

Main panel; Pilot panel

AZD5213 DRUG

Main panel

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and/or female volunteers between 20 to 45 years with suitable veins for cannulation or repeated venipuncture (pilot panel)
• Female must be of non-child bearing potential (pilot panel)
• BMI between 18 to 30 30 kg/m2
• Normal MRI scan
• Provision of signed, written and dated informed consent

You may not qualify if:

• History of any clinically significant disease or disorder
• History or presence of gastrointestinal, hepatic or renal disease
• Prolonged QTcF \>450 ms or shortened QTcF \<340 ms or family history of long QT syndrome
• History of severe allergy or hypersensitivity or ongoing allergy or hypersensitivity
• Healthy volunteer suffers from claustrophobia

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Uppsala, Sweden

Location

Related Publications (1)

• Jucaite A, Takano A, Bostrom E, Jostell KG, Stenkrona P, Halldin C, Segerdahl M, Nyberg S. AZD5213: a novel histamine H3 receptor antagonist permitting high daytime and low nocturnal H3 receptor occupancy, a PET study in human subjects. Int J Neuropsychopharmacol. 2013 Jul;16(6):1231-9. doi: 10.1017/S1461145712001411. Epub 2012 Dec 10.

  PMID: 23217964 DERIVED

Related Links

• D3030C00003 Clinical Study Report Synopsis

Study Officials

• Björn Paulsson, MD

  AstraZeneca

  STUDY DIRECTOR

• Wolfgang Kühn, MD

  Quintiles AB, Uppsala

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2010
• First Posted: September 3, 2010
• Study Start: November 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: January 28, 2015

Record last verified: 2015-01

Locations

SE (1)