Study of APD421 as PONV Treatment (Prior Prophylaxis)

NCT02646566 | Completed Phase 3 Results DMC

• 1 other identifier: DP10019
• Study Type: interventional
• Target: 705
• Locations: 3 countries
• Sites: 8

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 had prior PONV prophylaxis.

Conditions

Postoperative Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

• Number of Participants With 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 administration of study medication

Secondary Outcomes (10)

• Number of Participants With Complete Response 0-2 Hrs

  0-2 hours after administration of study medication

• Number of Participants With Complete Response 0-4 Hrs

  0-4 hours after administration of study medication

• Number of Participants With Complete Response 0-6 Hrs

  0-6 hours after administration of study medication

• Time to Treatment Failure

  0-24 hours after study drug administration

• Number of Patients With Incidence of Emesis

  30 mins to 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 moderate or high 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 (wound closure) 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 dopamine-antagonist agent likely to prevent or treat nausea or vomiting (given as prophylaxis or otherwise) in the period from 24 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 with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or breast cancer) or phaeochromocytoma.
• Patients with documented or suspected alcohol or substance abuse within the past 6 months.
• Patients with direct or indirect evidence of clinically significant hypokalaemia, such as a serum potassium level \< 3.0 mmol/L.
• Patients who have received in the post-operative period, and prior to receiving study drug, any medication with a substantial risk of inducing 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, etc.
• Patients who have a documented, clinically significant cardiac arrhythmia or congenital long QT syndrome.
• Patients who are pregnant or breast feeding.
• Patients being treated with levodopa.
• 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.

Sponsors & Collaborators

• Acacia Pharma Ltd: lead

Study Sites (8)

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

CHU de Hautepierre

Strasbourg, France

Location

HELIOS Klinikum Aue

Aue, 08280, Germany

Location

Universität Heidelberg

Heidelberg, Germany

Location

Philipps University

Marburg, Germany

Location

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 with this study

Results Point of Contact

• Title: Dr Gabriel Fox
• Organization: Acacia Pharma

GabrielFox@acaciapharma.com

01223875919764

Study Officials

• Gabriel Fox, MB BChir

  Acacia Pharma Ltd

  STUDY DIRECTOR

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: January 4, 2016
• First Posted: January 5, 2016
• Study Start: March 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: January 22, 2019
• Results First Posted: December 19, 2018

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); US (4); FR (1)