Study of APD403 in the prevention of sickness caused by some chemotherapy drugs

Phase 1

Conditions: Chemotherapy-induced nausea and vomiting
MedDRA version: 16.1Level: LLTClassification code 10049091Term: Chemotherapy antiemetic prophylaxisSystem Organ Class: 100000004865
Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

Registration Number: EUCTR2013-001635-51-DK

Lead Sponsor: Acacia Pharma Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 315

Inclusion Criteria

1.Male or female patients = 18 years of age
2.Ability and willingness to give written informed consent
3.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)
4.Karnofsky performance score = 60%
5.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
6.Adequate haematological function
•Haemoglobin = 8 g/dL
•White blood count = 3.0 x 109/L
•Platelet count = 100 x 109/L
7.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

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 115

Exclusion Criteria

1.Patients scheduled to receive, prior to or in the 24 hours after cisplatin or AC, any other chemotherapeutic agent with a high or moderate emetic risk
2.Patients who have previously received anti-neoplastic chemotherapy
3.Patients scheduled to receive paclitaxel or docetaxel during the first cycle of their chemotherapy
4.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
5.Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or confirmed prolactin-dependent breast cancer) or phaeochromocytoma
6.Patients receiving amisulpride for any indication within the last 2 weeks
7.Patients who are allergic to amisulpride or any of the excipients of APD421; or to ondansetron, fosaprepitant or dexamethasone; or who would be otherwise considered inappropriate for treatment with any of those agents
8.Patients with a pre-existing vestibular disorder
9.Patients being treated with regular anti-emetic therapy including corticosteroids
10.Patients receiving inhaled corticosteroids, unless started more than one month prior to the expected date of study entry
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 receiving benzodiazepines, unless on a stable dose for at least one month prior to the expected date of study entry
14.Patients with pre-existing nausea or vomiting in the 24 hours before receiving chemotherapy
15.Patients who are pregnant or breast feeding
16.Patients with a history of alcohol abuse
17.Patients with any pre-existing, clinically significant cardiac arrhythmia
18.Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
19.Patients who have participated in another therapeutic study within the previous 28 days

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine how effective APD403 is at different doses at preventing sickness in patients given chemotherapy and to see if there is any relationship between the effectiveness and the dose.;Secondary Objective: To look at the severity and timescale of any sickness seen in patients receiving chemotherapy who have been given APD403 (at various doses), and to assess the safety of APD403 at various doses.;Primary end point(s): The primary outcome measure will be complete response in the delayed phase, described as a documented absence of emetic episodes and no rescue medication use in the period from 24:01 hours to 120:00 hours after the start of the (first) chemotherapy infusion.;Timepoint(s) of evaluation of this end point: 24:01 hours to 120:00 hours after the start of the (first) chemotherapy infusion

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy:<br>•CR in the acute phase (0-24 hours after the initiation of chemotherapy) and the overall phase (0-120 hours after the initiation of chemotherapy)<br>•Delayed phase CR in the subsets of patients who did and who did not achieve CR in the acute phase<br>•Separately in the acute, delayed and overall phases:<br>oIncidence of vomiting/retching<br>oIncidence and severity (measured on a 100 mm VAS) of any nausea (score >5 mm) and significant nausea (score >25 mm)<br>oUse of rescue medication<br>•Time to first emetic episode<br>•Time to first use of rescue medication<br>•Time to first incidence of significant nausea<br>•The above endpoints separately in the strata of cisplatin and AC patients<br>Safety: <br>•Nature and frequency of adverse events, laboratory and ECG abnormalities<br>;Timepoint(s) of evaluation of this end point: Up to 120 hours after the start of the (first) chemotherapy infusion

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