Phase II Dose-ranging Study of APD421 in PONV

NCT ID: NCT01510704

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 215 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2012-04-30

Brief Summary

To assess the efficacy and safety of different doses of APD421 in the prevention of post-operative nausea and vomiting (PONV) in adult patients at moderate to high-risk of PONV. Patients must be undergoing elective surgery under general anaesthesia (hysterectomy (any surgical technique), cholecystectomy (any surgical technique) or "other" elective surgery scheduled to last at least one hour from induction of anaesthesia), requiring at least one overnight stay in hospital, and have at least 2 of the following risk factors for PONV: Past history of PONV and/or motion sickness; Non-smoking status; Female gender; Planned opiate use for post-operative analgesia.

Conditions

Postoperative Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

IV

Low dose APD421

1mg dose level

Group Type: EXPERIMENTAL

APD421

Intervention Type: DRUG

IV

Mid Dose APD421

5mg dose level

Group Type: EXPERIMENTAL

APD421

Intervention Type: DRUG

IV

High Dose APD421

20mg dose level

Group Type: EXPERIMENTAL

APD421

Intervention Type: DRUG

IV

Interventions

APD421

IV

Intervention Type: DRUG

Placebo

IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female patients ≥ 18 years of age

2. Ability and willingness to give written informed consent

3. Patients undergoing elective surgery under general anaesthesia requiring at least one overnight stay in hospital for either:

1. Hysterectomy (any surgical technique)

2. Cholecystectomy (any surgical technique)

3. Other elective surgery requiring overnight admission to hospital and scheduled to last at least 1 hour from induction of anaesthesia

4. Patients with at least 2 of the following risk factors for PONV:

1. Past history of PONV and/or motion sickness

2. Habitual non-smoking status

3. Female sex

4. Expected to receive opioid analgesia post-operatively

5. American Society of Anesthesiologists (ASA) risk score I-III

6. Adequate cardiac, hepatic and renal function

• QTc interval < 500 ms
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 5 x upper limit normal (ULN)
• Bilirubin < 3 x ULN
• Creatinine < 2 x ULN

7. Adequate haematological function

• Haemoglobin ≥ 9 g/dL
• White blood count ≥ 3.0 x 109/L
• Platelet count ≥ 100 x 109/L

8. For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (e.g., abstinence from sexual intercourse, surgical sterilisation (of subject or partner) or a double-barrier method of contraception such as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in conjunction with partner's use of a condom) between the date of screening and at least 48 hours after administration of study drug.

Exclusion Criteria

1. Patients undergoing outpatient/day case surgery

2. Patients undergoing surgery where the patient is expected to remain ventilated for a period after surgery

3. Patients undergoing intra-thoracic, transplant or central nervous system surgery

4. Patients receiving a local anaesthetic/regional neuraxial (intrathecal or epidural) block

5. Patients who are expected to need a naso- or oral-gastric tube in situ after surgery is completed

6. Patients receiving the active ingredient of APD421 for any indication within the last 2 weeks

7. Patients who are allergic to the active ingredient or any of the excipients of APD421

8. Patients with a pre-existing vestibular disorder or history of dizziness

9. Patients with pre-existing nausea or vomiting in the 24 hours before surgery

10. Patients treated with regular anti-emetic therapy including corticosteroids

11. Patients being treated with medications which could induce torsades de pointes, including Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide; Class III antiarrhythmic agents such as amiodarone and sotalol; and other medications such as bepridil, cisapride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin

12. Patients being treated with levodopa

13. Patients who are pregnant or breast feeding

14. Patients with a history of alcohol abuse

15. Patients with pre-existing, clinically significant cardiac arrhythmia

16. Patients diagnosed with Parkinson's disease

17. Patients who have received anti-cancer chemotherapy in the previous 4 weeks

18. Patients with a history of epilepsy

19. Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study

20. Patients who have participated in a previous study within the last 28 days (French sites only: Patients who have participated in a previous study within the last 6 months, if required by national or local regulations)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Acacia Pharma Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Kranke, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals of Würzburg

Locations

Duke University Medical Center

Durham, North Carolina, United States

University Hospital

Besançon, , France

Hôpital mère enfant

Bron, , France

Hôpital Huriez

Lille, , France

University Hospital

Nancy, , France

Hôpital FOCH

Paris, , France

Hautepierre Hospital

Strasbourg, , France

HELIOS Klinikum Aue

Aue, , Germany

Charité - Universitätsmedizin

Berlin, , Germany

Universität Heidelberg

Heidelberg, , Germany

Klinikum Ludwigshafen

Ludwigshafen, , Germany

Philipps University

Marburg, , Germany

University Hospitals of Würzburg

Würzburg, , Germany

Countries

United States; France; Germany

References

Kranke P, Eberhart L, Motsch J, Chassard D, Wallenborn J, Diemunsch P, Liu N, Keh D, Bouaziz H, Bergis M, Fox G, Gan TJ. I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial. Br J Anaesth. 2013 Dec;111(6):938-45. doi: 10.1093/bja/aet251. Epub 2013 Jul 19.

Reference Type: DERIVED

PMID: 23872464 (View on PubMed)

Other Identifiers

DP10006

Identifier Type: -

Identifier Source: org_study_id