Open-label, ascending-dose, Phase II study to determine the minimum effective dose of APD421 (intravenous amisulpride) in the prevention of cisplatin-induced nausea and vomiting - Phase II proof-of-concept study of APD421

• Register: EUCTR
• Last refreshed on: 18 September 2012
• Main ID: EUCTR2010-022170-14-GB
• Date of registration: 23/11/2010
• Prospective Registration: Yes
• Primary sponsor: Acacia Pharma Ltd
• Public title: Open-label, ascending-dose, Phase II study to determine the minimum effective dose of APD421 (intravenous amisulpride) in the prevention of cisplatin-induced nausea and vomiting - Phase II proof-of-concept study of APD421
• Scientific title: Open-label, ascending-dose, Phase II study to determine the minimum effective dose of APD421 (intravenous amisulpride) in the prevention of cisplatin-induced nausea and vomiting - Phase II proof-of-concept study of APD421
• Date of first enrolment: 16/12/2010
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022170-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

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, a first cisplatin chemotherapy infusion at a dose of 50 mg/m2 or greater.
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 < 3 x ULN
• Creatinine < 2 x ULN.
6. Adequate haematological function
• Haemoglobin = 9 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 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Patients scheduled to receive, prior to or in the 24 hours after cisplatin, any chemotherapeutic agent with a high or moderate emetic risk according to published criteria.
2. Patients scheduled to receive paclitaxel or docetaxel.
3. 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 administration.
4. Patients receiving amisulpride for any indication within the last 2 weeks.
5. Patients who are allergic to amisulpride or any of the excipients of APD421.
6. Patients with a pre-existing vestibular disorder.
7. Patients being treated with regular anti-emetic therapy including corticosteroids.
8. Patients receiving inhaled corticosteroids, unless started more than one month prior to the expected date of study entry.
9. 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.
10. Patients being treated with levodopa.
11. Patients receiving benzodiazepines, unless on a stable dose for at least one month prior to the expected date of study entry.
12. Patients with pre-existing nausea or vomiting in the 24 hours before receiving cisplatin chemotherapy, e.g. anticipatory emesis.
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. Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study.
17. Patients who have participated in another study within the previous 28 days.
18. Patients who are allergic to ondansetron or who would otherwise be considered inappropriate to receive ondansetron.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cisplatin-induced nausea and vomiting
MedDRA version: 14.0 Level: PT Classification code 10054133 Term: Prophylaxis of nausea and vomiting System Organ Class: 10042613 - Surgical and medical procedures

Intervention(s)

Product Name: Amisulpride
Product Code: APD421
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AMISULPRIDE
CAS Number: 71675-85-9
Current Sponsor code: APD421
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Main Objective: To determine the lowest dose of APD421 which shows an adequate level of effectiveness at preventing sickness in patients given cisplatin chemotherapy (compared to what would be expected based on historical data on other known anti-emetics).

Primary end point(s): The primary outcome measure is complete response, described as an absence of emetic episodes and no rescue medication use in the 24-hour period after the start of the cisplatin infusion.

Secondary Objective: To quantify the severity and timescale of any sickness seen in patients given APD421 (at various doses) before cisplatin chemotherapy, and to assess the safety of APD421 at various doses.

Secondary ID(s)

DN10007