Open-label, Ascending-dose, Phase II Study to Determine the Minimum Effective Dose of APD421 in the Prevention of Cisplatin-induced Nausea and Vomiting

Phase II Proof-of-concept Study of APD421

Sponsors

Lead sponsor: Acacia Pharma Ltd

Source Acacia Pharma Ltd
Brief Summary

Evaluation of efficacy of APD421 in preventing nausea and vomiting caused by cisplatin

Overall Status Completed
Start Date February 2011
Completion Date July 2012
Primary Completion Date July 2012
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Complete Response 24 hours after cisplatin dosing
Enrollment 51
Condition
Intervention

Intervention type: Drug

Intervention name: APD421

Description: Single dose

Arm group label: APD421 starting dose

Eligibility

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.

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, see Appendix 4.

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 APD421 for any indication within the last 2 weeks

5. Patients who are allergic to APD421 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 xxx

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Location
facility
Herlev Hospital | Copenhagen, Denmark
Rigshospitalet | Copenhagen, Denmark
Odense University Hospital | Odense, Denmark
University Hospital of South Manchester NHS Trust | Manchester, United Kingdom
Location Countries

Denmark

United Kingdom

Verification Date

September 2012

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: APD421 starting dose

Arm group type: Experimental

Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Prevention

Masking: None (Open Label)

Source: ClinicalTrials.gov