Study of APD421 as PONV Treatment (no Prior Prophylaxis)

NCT02449291 | Completed Phase 3 Results DMC

• 1 other identifier: DP10018
• Study Type: interventional
• Target: 568
• Locations: 3 countries
• Sites: 4

Brief Summary

Double-blind, randomised, parallel-group, placebo-controlled, adaptive, seamless, dose-selecting study to compare the efficacy of APD421 to placebo as treatment of established PONV, in patients who have not had prior PONV prophylaxis.

Conditions

Postoperative Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

• Complete Response (Success of Initial PONV Treatment)

  The primary efficacy variable was the dichotomous variable: success or failure of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes\* to 24 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 24-hour period after administration of study medication.

  0-24 hours after treatment

Secondary Outcomes (9)

• Number of Participants With Complete Response 0-2 Hrs

  0-2 hours after administration of study medication

• Number of Participants With Complete Response 2-24 Hrs

  2-24 hours after administration of study medication

• Time to Treatment Failure

  0-24 hours after study drug administration

• Number of Patients Experiencing Incidence of Emesis

  30 mins to 24 hours after study drug administration

• Number of Participants Using Rescue Medication

  0-24 hours after study drug administration

Study Arms (3)

APD421 standard

EXPERIMENTAL

Single (standard) dose IV APD421

Drug: APD421

APD421 high

EXPERIMENTAL

Single (high) dose IV APD421

Drug: APD421

Placebo

PLACEBO COMPARATOR

Single IV placebo

Drug: Placebo

Interventions

APD421 DRUG

APD421 high; APD421 standard

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age
• Provision of written informed consent
• Patients scheduled to undergo elective surgery (open or laparoscopic technique) under general anaesthesia (other than total intravenous anaesthesia with propofol) expected to last at least one hour from induction of anaesthesia to extubation
• Patients judged by the investigator to have a low to moderate risk of experiencing PONV. In forming this judgment, investigators should pay particular attention to risk factors such as a past history of PONV and/or motion sickness; habitual non-smoking status; female sex; and likely use of opioid analgesia post-operatively
• For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (as defined in ICH M3 guidance, e.g., abstinence from sexual intercourse, surgical sterilisation (of subject or partner), combined oral contraceptive pill, 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, or any other method or combination of methods with a failure rate generally considered to be \<1% per year) between the date of screening and at least 48 hours after administration of study drug
• In order to be eligible for randomisation, subjects must also:
• (i) have experienced a first episode of PONV not more than 24 hours after the end of their operation and prior to discharge from hospital ("qualifying PONV episode"), for which they have not already received any anti-emetic treatment; and (ii) not have received any agent likely to prevent or treat nausea or vomiting (given as prophylaxis or otherwise) in the period from 12 hours prior to the start of their operation up to the time of the qualifying PONV episode.

You may not qualify if:

• Patients scheduled to undergo transplant surgery or any surgery where post-operative emesis may pose a significant danger to the patient
• Patients planned to receive only a local anaesthetic and/or regional neuraxial (intrathecal or epidural) block
• Patients who have received APD421 active ingredient for any indication within the last 2 weeks
• Patients who are allergic to APD421 active ingredient or any of the excipients of APD421
• Patients with a significant, ongoing history of vestibular disease or dizziness
• Patients being treated with regular anti-emetic therapy (dosed at least three times per week), which is still ongoing within one week prior to surgery
• Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or breast cancer) or phaeochromocytoma
• Patients being treated with levodopa
• Patients who are pregnant or breast feeding
• Patients with documented or suspected alcohol or substance abuse within the past 6 months
• Patients with a documented, clinically significant cardiac arrhythmia
• Patients diagnosed with Parkinson's disease
• Patients who have received emetogenic anti-cancer chemotherapy in the previous 4 weeks
• Patients with a history of epilepsy
• Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study

Sponsors & Collaborators

• Acacia Pharma Ltd: lead

Study Sites (4)

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

CHU de Hautepierre

Strasbourg, France

Location

Universität Heidelberg

Heidelberg, Germany

Location

Related Publications (1)

• Candiotti KA, Kranke P, Bergese SD, Melson TI, Motsch J, Siddiqui N, Chung F, Rodriguez Y, Minkowitz HS, Ayad SS, Diemunsch P, Fox G. Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis. Anesth Analg. 2019 Jun;128(6):1098-1105. doi: 10.1213/ANE.0000000000003733.

  PMID: 31094774 DERIVED

MeSH Terms

Conditions

Postoperative Nausea and Vomiting

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nausea; Signs and Symptoms, Digestive; Signs and Symptoms; Vomiting

Limitations and Caveats

There were no limitations or caveats associated with this study.

Results Point of Contact

• Title: Gabriel Fox
• Organization: Acacia Pharma Ltd

gabrielfox@acaciapharma.com

01-223919764

Study Officials

• Keith Candiotti, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2015
• First Posted: May 20, 2015
• Study Start: September 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: January 22, 2019
• Results First Posted: December 19, 2018

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); DE (1); US (2)