Phase II Dose-ranging Study of APD421 in PONV

• Sponsor: Acacia Pharma Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01510704
• Collaborator: (none)
• Enrollment: 215
• Locations: 13
• Arms: 4
• Duration (Months): 3
• Patients Per Site: 16.5
• Patients Per Site Per Month: 5.5

Study Details

Study Description

Brief Summary

To assess the efficacy and safety of different doses of APD421 in the prevention of post-operative nausea and vomiting (PONV) in adult patients at moderate to high-risk of PONV. Patients must be undergoing elective surgery under general anaesthesia (hysterectomy (any surgical technique), cholecystectomy (any surgical technique) or "other" elective surgery scheduled to last at least one hour from induction of anaesthesia), requiring at least one overnight stay in hospital, and have at least 2 of the following risk factors for PONV: Past history of PONV and/or motion sickness; Non-smoking status; Female gender; Planned opiate use for post-operative analgesia.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Nausea and Vomiting	Drug: APD421; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 215 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomised, Double-blind, Placebo-controlled, Dose-ranging Phase II Study of APD421 for the Prevention of Post-operative Nausea and Vomiting
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; IV
Experimental: Low dose APD421 1mg dose level	Drug: APD421; IV
Experimental: Mid Dose APD421 5mg dose level	Drug: APD421; IV
Experimental: High Dose APD421 20mg dose level	Drug: APD421; IV

Outcome Measures

Primary Outcome Measures

1. Post-operative Nausea or Vomiting [24 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

1. Male or female patients ≥ 18 years of age

2. Ability and willingness to give written informed consent

3. Patients undergoing elective surgery under general anaesthesia requiring at least one overnight stay in hospital for either:

4. Hysterectomy (any surgical technique)

5. Cholecystectomy (any surgical technique)

6. Other elective surgery requiring overnight admission to hospital and scheduled to last at least 1 hour from induction of anaesthesia

7. Patients with at least 2 of the following risk factors for PONV:

8. Past history of PONV and/or motion sickness

9. Habitual non-smoking status

10. Female sex

11. Expected to receive opioid analgesia post-operatively

12. American Society of Anesthesiologists (ASA) risk score I-III

13. 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

1. Adequate haematological function

• Haemoglobin ≥ 9 g/dL

• White blood count ≥ 3.0 x 109/L

• Platelet count ≥ 100 x 109/L

1. 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) between the date of screening and at least 48 hours after administration of study drug.

Exclusion Criteria

1. Patients undergoing outpatient/day case surgery

2. Patients undergoing surgery where the patient is expected to remain ventilated for a period after surgery

3. Patients undergoing intra-thoracic, transplant or central nervous system surgery

4. Patients receiving a local anaesthetic/regional neuraxial (intrathecal or epidural) block

5. Patients who are expected to need a naso- or oral-gastric tube in situ after surgery is completed

6. Patients receiving the active ingredient of APD421 for any indication within the last 2 weeks

7. Patients who are allergic to the active ingredient or any of the excipients of APD421

8. Patients with a pre-existing vestibular disorder or history of dizziness

9. Patients with pre-existing nausea or vomiting in the 24 hours before surgery

10. Patients treated with regular anti-emetic therapy including corticosteroids

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 who are pregnant or breast feeding

14. Patients with a history of alcohol abuse

15. Patients with pre-existing, clinically significant cardiac arrhythmia

16. Patients diagnosed with Parkinson's disease

17. Patients who have received anti-cancer chemotherapy in the previous 4 weeks

18. Patients with a history of epilepsy

19. Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study

20. Patients who have participated in a previous study within the last 28 days (French sites only: Patients who have participated in a previous study within the last 6 months, if required by national or local regulations)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710
2	University Hospital	Besançon		France
3	Hôpital mère enfant	Bron		France	69500
4	Hôpital Huriez	Lille		France
5	University Hospital	Nancy		France
6	Hôpital FOCH	Paris		France
7	Hautepierre Hospital	Strasbourg		France	67000
8	HELIOS Klinikum Aue	Aue		Germany
9	Charité - Universitätsmedizin	Berlin		Germany
10	Universität Heidelberg	Heidelberg		Germany
11	Klinikum Ludwigshafen	Ludwigshafen		Germany
12	Philipps University	Marburg		Germany
13	University Hospitals of Würzburg	Würzburg		Germany

Sponsors and Collaborators

• Acacia Pharma Ltd

Investigators

• Principal Investigator: Peter Kranke, MD, University Hospitals of Würzburg

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acacia Pharma Ltd
• ClinicalTrials.gov Identifier: NCT01510704
• Other Study ID Numbers: DP10006
• First Posted: Jan 16, 2012
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Nausea; Vomiting; Postoperative Nausea and Vomiting

Study Results

Participant Flow

Arm/Group Title	Placebo	Low Dose APD421	Mid Dose APD421	High Dose APD421
Arm/Group Description	Single-dose IV placebo	Single-dose 1 mg IV APD421	Single-dose 5 mg IV APD421	Single-dose 20 mg IV APD421
Period Title: Overall Study
STARTED	54	58	50	53
COMPLETED	54	58	50	53
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Low Dose APD421	Mid Dose APD421	High Dose APD421	Total
Arm/Group Description	1mg dose level	5mg dose level	20mg dose level	Total of all reporting groups
Overall Participants	54	58	50	53	215
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.1 (13.6)	50 (14.5)	50 (16.2)	50.7 (15.7)	49.9 (14.9)
Sex: Female, Male (Count of Participants)
Female	47 87%	53 91.4%	48 96%	49 92.5%	197 91.6%
Male	7 13%	5 8.6%	2 4%	4 7.5%	18 8.4%

Outcome Measures

1. Primary Outcome

Title	Post-operative Nausea or Vomiting
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	Low Dose APD421	Mid Dose APD421	High Dose APD421
Arm/Group Description	1mg dose level	5mg dose level	20mg dose level
Measure Participants	54	58	50	53
Number [participants]	37 68.5%	28 48.3%	20 40%	30 56.6%

Adverse Events

Arm/Group Title	Placebo		Low Dose APD421		Mid Dose APD421		High Dose APD421
Arm/Group Description	1mg dose level		5mg dose level		20mg dose level
All Cause Mortality
	Placebo		Low Dose APD421		Mid Dose APD421		High Dose APD421
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Low Dose APD421		Mid Dose APD421		High Dose APD421
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/54 (3.7%)		1/58 (1.7%)		0/50 (0%)		2/53 (3.8%)
Injury, poisoning and procedural complications
POST PROCEDURAL HAEMATOMA	0/54 (0%)	0	1/58 (1.7%)	1	0/50 (0%)	0	1/53 (1.9%)	1
Procedural pain	1/54 (1.9%)	1	0/58 (0%)	0	0/50 (0%)	0	0/53 (0%)	0
POST PROCEDURAL HAEMORRHAGE	0/54 (0%)	0	0/58 (0%)	0	0/50 (0%)	0	1/53 (1.9%)	1
WOUND HAEMATOMA	1/54 (1.9%)	1	0/58 (0%)	0	0/50 (0%)	0	0/53 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Low Dose APD421		Mid Dose APD421		High Dose APD421
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/54 (96.3%)		50/58 (86.2%)		39/50 (78%)		46/53 (86.8%)
Gastrointestinal disorders
Nausea	28/54 (51.9%)	28	19/58 (32.8%)	19	13/50 (26%)	13	24/53 (45.3%)	24
Vomiting	18/54 (33.3%)	18	14/58 (24.1%)	14	7/50 (14%)	7	9/53 (17%)	9
Constipation	6/54 (11.1%)	6	6/58 (10.3%)	6	6/50 (12%)	6	6/53 (11.3%)	6
Flatulence	7/54 (13%)	7	7/58 (12.1%)	7	4/50 (8%)	4	4/53 (7.5%)	4
General disorders
Pain	5/54 (9.3%)	5	7/58 (12.1%)	7	3/50 (6%)	3	6/53 (11.3%)	6
Injury, poisoning and procedural complications
Procedural Pain	28/54 (51.9%)	28	30/58 (51.7%)	30	27/50 (54%)	27	27/53 (50.9%)	27
Procedural nausea	5/54 (9.3%)	5	4/58 (6.9%)	4	4/50 (8%)	4	5/53 (9.4%)	5
Psychiatric disorders
Insomnia	1/54 (1.9%)	1	3/58 (5.2%)	3	5/50 (10%)	5	4/53 (7.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.