Clinical trial NCT00984880: Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD3043
Official title: Phase I, Single Centre, Open Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous AZD3043 After a Single Ascending Bolus Dose, and a Single Ascending Bolus Dose Followed by a Single Infusion Dose in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Sedation
anaesthesia
Safety
Tolerability
Pharmacokinetics
Pharmacodynamics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-09-25
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to assess the safety and tolerability of AZD3043 following administration of single ascending bolus doses (Part A) and single ascending bolus doses followed by infusion (Part B).


Eligibility criteria: Inclusion Criteria:

* Subjects with suitable veins for cannulation or repeated venepuncture
* Pre-dose assessment judged without remarks by the investigator
* Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg

Exclusion Criteria:

* Abnormal vital signs, after 15 minutes supine rest, defined as any of the following:
* Systolic blood pressure \>140 mm Hg
* Diastolic blood pressure \>90 mm Hg
* Heart rate ≤45 or \>85 beats per minute
* Lack of normal phenotype for BuChE (Butyrylcholinesterase)

Primary outcomes:
measure: Assessment of vital signs data, heart rate, ECG
timeFrame: The measure will be taken between -20 to 120 min relative to stop of administration of AZD3043
measure: Respiratory signs data (SpO2, EtCO2, PaO2, blood gases, respiratory frequency and pattern, occurrence of apnoea)
timeFrame: The measure will be taken between -20 to 120 min relative to stop of administration of AZD3043
Secondary outcomes:
measure: PK parameters for AZD3043: Cmax (in part B: bolus Cmax and infusion Cmax), AUClast, AUC, lz, t½lz, CL, Vc, Vss, Vz, tmax, tlast and MRT arterial and venous plasma.
timeFrame: Part A: Arterial: Predose and continously up to 120 min after start of dosing. Part B: Arterial: Predose and continously up to 150 min after start of dosing. Venous: Predose and continously up to 24 h after start of dosing
measure: PK parameters for the metabolite (THRX 108893): Cmax (in part B: bolus Cmax and infusion Cmax), AUClast, AUC, tmax, tlast, lz and t½lz in arterial and venous plasma.
timeFrame: Part A: Arterial: Predose and continously up to 120 min after start of dosing. Part B: Arterial: Predose and continously up to 150 min after start of dosing. Venous: Predose and continously up to 24 h after start of dosing
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Johan Wemer
role: STUDY_CHAIR
affiliation: Karolinska University Hospital
name: Sigridur Kalman
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Stephen Kanes
role: STUDY_DIRECTOR
References:
citation: Norberg A, Koch P, Kanes SJ, Bjornsson MA, Barassin S, Ahlen K, Kalman S. A Bolus and Bolus Followed by Infusion Study of AZD3043, an Investigational Intravenous Drug for Sedation and Anesthesia: Safety and Pharmacodynamics in Healthy Male and Female Volunteers. Anesth Analg. 2015 Oct;121(4):894-903. doi: 10.1213/ANE.0000000000000804.