Dose-finding Study of APD403 to Prevent Nausea and Vomiting After Chemotherapy

NCT01857232 | Completed Phase 2 Results DMC

• 1 other identifier: DN10016
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 1

Brief Summary

Comparison of efficacy of APD403 at preventing delayed sickness in patients who have received cancer chemotherapy

Conditions

CINV

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Delayed Phase Complete Response(CR)

  Delayed phase complete response (CR), defined as an absence of emetic episodes and no rescue medication use in the period from 24 to 120 hours after the initiation of chemotherapy. The primary endpoint was analysed separately in the strata of chemotherapy regimen and gender, and in the strata of country.

  24-120 hours

Secondary Outcomes (1)

• Number of Participants With CR in the Overall Phase.

  0 to 120 hours after the initiation of chemotherapy

Study Arms (5)

Control

OTHER

OND + DEX + FOS followed by oral DEX

Drug: Ondansetron; Drug: Dexamethasone; Drug: Fosaprepitant

Placebo

PLACEBO COMPARATOR

OND + APD403 followed by oral PLACEBO

Drug: Ondansetron; Drug: Placebo; Drug: APD403 IV

Low dose APD403

EXPERIMENTAL

OND + APD403 followed by oral APD403 low dose

Drug: Ondansetron; Drug: APD403 IV; Drug: APD403 oral

Mid dose APD403

EXPERIMENTAL

OND + APD403 followed by oral APD403 mid dose

Drug: Ondansetron; Drug: APD403 IV; Drug: APD403 oral

High dose APD403

EXPERIMENTAL

OND + APD403 followed by oral APD403 high dose

Drug: Ondansetron; Drug: APD403 IV; Drug: APD403 oral

Interventions

Ondansetron DRUG

5HT3-antagonist

Control; High dose APD403; Low dose APD403; Mid dose APD403; Placebo

Placebo DRUG

Comparator

Placebo

Dexamethasone DRUG

Corticosteroid

Control

Fosaprepitant DRUG

NK1 antagonist

Control

APD403 IV DRUG

Amisulpride IV 20 mg

High dose APD403; Low dose APD403; Mid dose APD403; Placebo

APD403 oral DRUG

Amisulpride oral 10, 20 or 40 mg

High dose APD403; Low dose APD403; Mid dose APD403

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
• Ability and willingness to give written informed consent
• Patients scheduled to receive, on day 1 of their chemotherapy, either: (i) a first cisplatin chemotherapy infusion at a dose of ≥70 mg/m2 (males and females); or (ii) a first infusion of cyclophosphamide at a dose of 500-1500 mg/m2 in combination with either epirubicin at a dose of 60-100 mg/m2 or doxorubicin at a dose of 40-60 mg/m2 (females only)
• Karnofsky performance score ≥ 60%
• 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 \< 5 x ULN
• Creatinine \< 3 x ULN
• Adequate haematological function
• Haemoglobin ≥ 8 g/dL
• White blood count ≥ 3.0 x 109/L
• Platelet count ≥ 100 x 109/L
• 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) during the study and for a period of at least 48 hours afterwards

You may not qualify if:

• Patients scheduled to receive, prior to or in the 120 hours after cisplatin or AC, any other chemotherapeutic agent with a high or moderate emetic risk
• Patients who have previously received anti-neoplastic chemotherapy
• Patients scheduled to receive paclitaxel or docetaxel during the first cycle of their chemotherapy
• Patients undergoing abdominal or pelvic irradiation within 48 hours prior to screening or scheduled to receive abdominal or pelvic irradiation between screening and 24 hours after cisplatin or AC administration
• Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or confirmed prolactin-dependent breast cancer) or phaeochromocytoma
• Patients with a pre-existing vestibular disorder
• Patients being treated with regular anti-emetic therapy including corticosteroids
• Patients receiving inhaled corticosteroids, unless started more than one month prior to the expected date of study entry

Sponsors & Collaborators

• Acacia Pharma Ltd: lead

Study Sites (1)

Odense University Hospital

Odense, Denmark

Location

Related Publications (1)

• Herrstedt J, Summers Y, Jordan K, von Pawel J, Jakobsen AH, Ewertz M, Chan S, Naik JD, Karthaus M, Dubey S, Davis R, Fox GM. Amisulpride prevents nausea and vomiting associated with highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled, dose-ranging trial. Support Care Cancer. 2019 Jul;27(7):2699-2705. doi: 10.1007/s00520-018-4564-8. Epub 2018 Nov 28.

  PMID: 30488222 DERIVED

MeSH Terms

Interventions

Ondansetron; Dexamethasone; fosaprepitant

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

There were no limitations and caveats with this study

Results Point of Contact

• Title: Dr Gabriel Fox
• Organization: Acacia Pharma Ltd

GabrielFox@acaciapharma.com

+44-(0)1223-875149

Study Officials

• Jørn Herrstedt, MD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 20, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: November 25, 2020
• Results First Posted: March 12, 2019

Record last verified: 2020-11

Locations

DK (1)