Study of APD421 With and Without Ondansetron

A Randomised, Double-blind, Placebo-controlled, Crossover Study in Healthy Adult Subjects to Investigate the Effect of Intravenous APD421, With and Without Ondansetron, on Cardiac Conduction

Collection of pharmacokinetic and electrocardiograph data from healthy volunteers given APD421 +/- ondansetron

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: Placebo; Drug: APD421; Drug: Ondansetron

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy subjects
2. Age 18 to 65 years of age at time of signing ICF
3. Body mass index (BMI) of 18 to 30 kg/m2
4. Must be willing and able to communicate and participate in the whole study
5. Must provide written informed consent
6. Must agree to use an adequate method of contraception

Exclusion Criteria:

1. Subjects who have received any investigational medicinal product (IMP) in a clinical research study within the 3 months prior to IMP administration on this study
2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee
3. Subjects who have previously been enrolled in this study
4. Women who are pregnant or breastfeeding
5. Subjects who have received amisulpride for any indication within the previous 4 weeks
6. Allergy to amisulpride or any of the excipients of APD421 or ondansetron
7. History of any drug or alcohol abuse in the past 2 years
8. Regular alcohol consumption >21 units per week
9. Current smokers and those who have smoked within the last 12 months; this includes cigarettes, e-cigarettes and nicotine replacement products (current smoking may be assessed by a validated technique such as urine or serum cotinine levels)
10. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
11. History of epilepsy
12. History of clinically significant syncope
13. Family history of sudden death
14. Family history of premature cardiovascular death
15. Clinically significant history or family history of congenital long QT syndrome (e.g. Romano-Ward syndrome, Jervell and Lange-Nielson syndrome) or Brugada's syndrome
16. History of clinically significant arrhythmias or ischaemic heart disease (especially ventricular arrhythmias, atrial fibrillation (AF), recent conversion from AF or coronary spasm)
17. Conditions predisposing the volunteer to electrolyte imbalances (e.g. altered nutritional states, chronic vomiting, anorexia nervosa, bulimia nervosa)

18. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes.

    This includes subjects with any of the following at screening:

    • Absence of regular supraventricular rhythm
    • Clinically significant PR (PQ) interval prolongation
    • Intermittent second or third degree AV block
    • Incomplete or complete bundle branch block.
    • Abnormal T-wave morphology
    • Prolonged QTcB >450 ms or shortened QTcB < 350 ms or family history of long QT syndrome Subject with borderline deviations from these criteria may be included if the deviations do not pose a safety risk, as judged by the investigator

19. Clinically significant abnormal biochemistry, haematology or urinalysis at screening as judged by the investigator, especially:

    • Creatinine clearance (estimated using Cockcroft-Gault formula) < 60 mL/min
    • Alanine aminotransferase (ALT) > 1.5 x upper limit of normal or bilirubin > 3 x upper limit of normal
20. Positive drugs of abuse test result
21. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results at screening
22. Donation or loss of greater than 100 mL of blood within the 3 months prior to screening or planned blood donation during the study until after final visit
23. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IMP administration
24. Failure to satisfy the investigator of fitness to participate for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; IV
EXPERIMENTAL: APD421	Drug: APD421; 10 mg IV
EXPERIMENTAL: APD421 + ondansetron	Drug: APD421; 10 mg IV; Drug: Ondansetron; 4 mg IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ddQTcF	Placebo-corrected change-from-baseline QTcF interval	0-6 hours

Collaborators and Investigators

• Sponsor: Acacia Pharma Ltd
• Investigators: Principal Investigator: Muna Albayaty, Early Phase Clinical Unit

Publications and helpful links

General Publications

• Fox GM, Albayaty M, Walker JL, Xue H, Darpo B. Intravenous Amisulpride Does Not Meaningfully Prolong the QTc Interval at Doses Effective for the Management of Postoperative Nausea and Vomiting. Anesth Analg. 2021 Jan;132(1):150-159. doi: 10.1213/ANE.0000000000004538.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 17, 2018
• Primary Completion (ACTUAL): August 13, 2018
• Study Completion (ACTUAL): August 13, 2018

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (ACTUAL): July 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2018
• Last Update Submitted That Met QC Criteria: September 28, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Ondansetron
• Other Study ID Numbers: DP10022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No