CINVPhase 2NCT01857232

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

A Phase 2 study testing Ondansetron, Dexamethasone and Fosaprepitant in people with CINV, run by Acacia Pharma Ltd at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Comparison of efficacy of APD403 at preventing delayed sickness in patients who have received cancer chemotherapy Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: CINV
What is being tested?: Ondansetron, Dexamethasone and Fosaprepitant
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 342 participants
Where: 1 siteDenmark
Study dates: Oct 2013to Feb 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 14Show fewer

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

Odense University Hospital
Odense

Other trials in Denmark

About this study

Official title: Randomised, Double-blind, Dose-finding Phase II Study to Assess the Efficacy of APD403 in the Prevention of Nausea and Vomiting Caused by Cisplatin- or Anthracycline/Cyclophosphamide (AC)-Based Chemotherapy

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

Conditions: CINV
Being tested: Ondansetron, Placebo, Dexamethasone, Fosaprepitant, APD403 IV

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OndansetronDrug
5HT3-antagonist
PlaceboDrug
Comparator
DexamethasoneDrug
Corticosteroid
FosaprepitantDrug
NK1 antagonist
APD403 IVDrug
Amisulpride IV 20 mg
APD403 oralDrug
Amisulpride oral 10, 20 or 40 mg

Study groups in NCT01857232
Study group	Role	What they receive
Control	Other	OND + DEX + FOS followed by oral DEX Receives: Drug: Ondansetron; Drug: Dexamethasone; Drug: Fosaprepitant
Placebo	Placebo comparator	OND + APD403 followed by oral PLACEBO Receives: Drug: Ondansetron; Drug: Placebo; Drug: APD403 IV
Low dose APD403	Experimental	OND + APD403 followed by oral APD403 low dose Receives: Drug: Ondansetron; Drug: APD403 IV; Drug: APD403 oral
Mid dose APD403	Experimental	OND + APD403 followed by oral APD403 mid dose Receives: Drug: Ondansetron; Drug: APD403 IV; Drug: APD403 oral
High dose APD403	Experimental	OND + APD403 followed by oral APD403 high dose Receives: Drug: Ondansetron; Drug: APD403 IV; Drug: APD403 oral

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 24-120 hours

Secondary outcomes (1)

Number of Participants With CR in the Overall Phase.
CR defined as no emesis and no use of rescue medication, in the overall phase (0 to 120 hours after the initiation of chemotherapy)
Measured: 0 to 120 hours after the initiation of chemotherapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2013Feb 2015

First posted20 May 2013 (estimated)
Study startOct 2013
Primary completionFeb 2015
Study completionFeb 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for CINVStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 342 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01857232
Sponsor's protocol ID: DN10016
Status last verified: Nov 2020
First submitted: 16 May 2013
Last updated: 25 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 30488222

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
HR20013 for the Prevention of Nausea and Vomiting in Patients With Cancer: A Real-World Study
Chemotherapy-Induced Nausea and Vomiting (CINV), Nausea
RecruitingPhase 1
A Study to Compare the Bioavailability of Ondansetron Following Nasal (NS003) and IV Administration in Healthy Adults
Chemotherapy-Induced Nausea and Vomiting (CINV), Radiotherapy-induced Nausea and Vomiting (RINV)
RecruitingPhase 2
A Study to Evaluate LY3537021 for the Treatment of Nausea and Vomiting Caused by Chemotherapy in Adults With Cancer
Nausea, Vomiting
RecruitingPhase 2
Study With IV NEPA (Fosnetupitant/Palonosetron) for the Prevention of Chemotherapy-induced Nausea and Vomiting in Paediatric Cancer Patients Undergoing Highly Emetogenic Chemotherapy (HEC)
Nausea and Vomiting Chemotherapy-Induced, Nausea Post Chemotherapy
Active, not recruitingPhase 2
Fosrolapitant and Palonosetron for Highly Emetogenic ADC-Induced Nausea and Vomiting in Solid Tumors
Solid Tumor Cancer

All CINV trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomised, Double-blind, Dose-finding Phase II Study to Assess the Efficacy of APD403 in the Prevention of Nausea and Vomiting Caused by Cisplatin- or Anthracycline/Cyclophosphamide (AC)-Based Chemotherapy
ClinicalTrials.gov ID: NCT01857232
Acronym / sponsor ID: DN10016
Conditions: CINV
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 342 participants (actual)
Lead sponsor: Acacia Pharma LtdIndustry (pharma, biotech, devices)
Study start: Oct 2013
Primary completion: Feb 2015 (actual)
Study completion: Feb 2015 (actual)
First posted: 20 May 2013 (estimated)
Results: Posted 12 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Control	Other	Drug: Ondansetron, Drug: Dexamethasone, Drug: FosaprepitantOND + DEX + FOS followed by oral DEX
Placebo	Placebo comparator	Drug: Ondansetron, Drug: Placebo, Drug: APD403 IVOND + APD403 followed by oral PLACEBO
Low dose APD403	Experimental	Drug: Ondansetron, Drug: APD403 IV, Drug: APD403 oralOND + APD403 followed by oral APD403 low dose
Mid dose APD403	Experimental	Drug: Ondansetron, Drug: APD403 IV, Drug: APD403 oralOND + APD403 followed by oral APD403 mid dose
High dose APD403	Experimental	Drug: Ondansetron, Drug: APD403 IV, Drug: APD403 oralOND + APD403 followed by oral APD403 high dose

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ondansetron5HT3-antagonist	Drug	Control, High dose APD403, Low dose APD403, Mid dose APD403, Placebo
PlaceboComparator	Drug	Placebo
DexamethasoneCorticosteroid	Drug	Control
FosaprepitantNK1 antagonist	Drug	Control
APD403 IVAmisulpride IV 20 mg	Drug	High dose APD403, Low dose APD403, Mid dose APD403, Placebo
APD403 oralAmisulpride oral 10, 20 or 40 mg	Drug	High dose APD403, Low dose APD403, Mid dose APD403

Primary outcome

Number of Participants With Delayed Phase Complete Response(CR)
Time frame: 24-120 hours
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.

1 secondary outcome

Number of Participants With CR in the Overall Phase.
Time frame: 0 to 120 hours after the initiation of chemotherapy

Results and safety

Results posted to the registry on 12 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control	69	61
Placebo	67	65
APD403 10MG	67	63
APD403 20MG	70	68
ADP403 40MG	69	63

Primary outcome: Number of Participants With Delayed Phase Complete Response(CR)

Time frame: 24-120 hours. Count of participants. Unit: Participants

Measure	Control n = 66	PLACEBO n = 66	APD403 10MG n = 63	ADP421 20MG n = 68	APD421 40MG n = 65
Value	37	13	27	21	20

PLACEBO vs APD403 10MG: p = 0.004, Regression, Logistic
PLACEBO vs ADP421 20MG: p = 0.0987, Regression, Logistic
PLACEBO vs APD421 40MG: p = 0.1041, Regression, Logistic

Population analysed: ITT

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 7 Days. Other adverse events reported at 5.0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control	8 of 66 (12.1%)	36 of 66 (54.5%)	2 of 66
Placebo	12 of 66 (18.2%)	47 of 66 (71.2%)	0 of 66
APD403 10MG	2 of 63 (3.2%)	34 of 63 (54%)	0 of 63
APD403 20MG	3 of 68 (4.4%)	21 of 68 (30.9%)	0 of 68
ADP403 40MG	4 of 65 (6.2%)	28 of 65 (43.1%)	0 of 65

Limitations and caveats (from the sponsor): There were no limitations and caveats with this study

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30488222Herrstedt 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.

Related trials for CINV

RecruitingObservational study
HR20013 for the Prevention of Nausea and Vomiting in Patients With Cancer: A Real-World Study
Chemotherapy-Induced Nausea and Vomiting (CINV), Nausea
RecruitingPhase 1
A Study to Compare the Bioavailability of Ondansetron Following Nasal (NS003) and IV Administration in Healthy Adults
Chemotherapy-Induced Nausea and Vomiting (CINV), Radiotherapy-induced Nausea and Vomiting (RINV)
RecruitingPhase 2
A Study to Evaluate LY3537021 for the Treatment of Nausea and Vomiting Caused by Chemotherapy in Adults With Cancer
Nausea, Vomiting
RecruitingPhase 2
Study With IV NEPA (Fosnetupitant/Palonosetron) for the Prevention of Chemotherapy-induced Nausea and Vomiting in Paediatric Cancer Patients Undergoing Highly Emetogenic Chemotherapy (HEC)
Nausea and Vomiting Chemotherapy-Induced, Nausea Post Chemotherapy
Active, not recruitingPhase 2
Fosrolapitant and Palonosetron for Highly Emetogenic ADC-Induced Nausea and Vomiting in Solid Tumors
Solid Tumor Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jørn Herrstedt, MD principal investigator

Odense University Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ondansetron, Dexamethasone and Fosaprepitant in people with CINV, run by Acacia Pharma Ltd at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Delayed Phase Complete Response(CR) (time frame: 24-120 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01857232, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2020.