Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD3043

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: AZD3043


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Intravenous solution given as a single ascending bolus dose | Drug: AZD3043<br>* Intravenous solution given as bolus dose (part A) and as bolus dose followed by infusion (part B)<br>|
| Experimental: 2<br>Intravenous solution given as a single ascending bolus dose followed by a single infusion | Drug: AZD3043<br>* Intravenous solution given as bolus dose (part A) and as bolus dose followed by infusion (part B)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of vital signs data, heart rate, ECG |  | The measure will be taken between -20 to 120 min relative to stop of administration of AZD3043 | 
| Respiratory signs data (SpO2, EtCO2, PaO2, blood gases, respiratory frequency and pattern, occurrence of apnoea) |  | The measure will be taken between -20 to 120 min relative to stop of administration of AZD3043 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 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 | 
| 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. |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sedation, anaesthesia, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics