CINV
Conditions
Brief summary
Comparison of efficacy of APD403 at preventing delayed sickness in patients who have received cancer chemotherapy
Interventions
DRUGOndansetron
5HT3-antagonist
DRUGPlacebo
Comparator
DRUGDexamethasone
Corticosteroid
DRUGFosaprepitant
NK1 antagonist
DRUGAPD403 IV
Amisulpride IV 20 mg
DRUGAPD403 oral
Amisulpride oral 10, 20 or 40 mg
Sponsors
Acacia Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Delayed Phase Complete Response(CR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With CR in the Overall Phase. | 0 to 120 hours after the initiation of chemotherapy | CR defined as no emesis and no use of rescue medication, in the overall phase (0 to 120 hours after the initiation of chemotherapy) |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control ( Dexamethazon) ACUTE (day 1): IV OND + FOS + DEX
• DELAYED (days 2 to 4): Oral DEX | 66 |
| Placebo ACUTE (day 1): IV OND + APD403 20 mg DELAYED (days 2 to 4): Oral Placebo | 66 |
| APD403 10MG ACUTE (day 1): IV OND + APD403 20 mg
• DELAYED (days 2 to 4): Oral APD403 10 mg | 63 |
| APD403 20MG ACUTE (day 1): IV OND + APD403 20 mg
• DELAYED (days 2 to 4): Oral APD403 20 mg | 68 |
| ADP403 40MG ACUTE (day 1): IV OND + APD403 20 mg
• DELAYED (days 2 to 4): Oral APD403 40 mg | 65 |
| Total | 328 |
Baseline characteristics
| Characteristic | Total | Control ( Dexamethazon) | Placebo | APD403 10MG | APD403 20MG | ADP403 40MG |
|---|---|---|---|---|---|---|
| Age, Continuous | 57.1 Years STANDARD_DEVIATION 10.7 | 58.1 Years STANDARD_DEVIATION 10.38 | 57.3 Years STANDARD_DEVIATION 11.01 | 56.9 Years STANDARD_DEVIATION 11.24 | 56.6 Years STANDARD_DEVIATION 10.53 | 56.5 Years STANDARD_DEVIATION 10.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 323 Participants | 65 Participants | 64 Participants | 62 Participants | 68 Participants | 64 Participants |
| Region of Enrollment Denmark | 73 Participants | 16 Participants | 12 Participants | 13 Participants | 17 Participants | 15 Participants |
| Region of Enrollment Germany | 108 Participants | 23 Participants | 23 Participants | 19 Participants | 21 Participants | 22 Participants |
| Region of Enrollment United Kingdom | 147 Participants | 27 Participants | 31 Participants | 31 Participants | 30 Participants | 28 Participants |
| Sex: Female, Male Female | 257 Participants | 51 Participants | 51 Participants | 52 Participants | 52 Participants | 51 Participants |
| Sex: Female, Male Male | 71 Participants | 15 Participants | 15 Participants | 11 Participants | 16 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 66 | 0 / 66 | 0 / 63 | 0 / 68 | 0 / 65 |
| other Total, other adverse events | 36 / 66 | 47 / 66 | 34 / 63 | 21 / 68 | 28 / 65 |
| serious Total, serious adverse events | 8 / 66 | 12 / 66 | 2 / 63 | 3 / 68 | 4 / 65 |
Outcome results
Primary
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.
Time frame: 24-120 hours
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Participants With Delayed Phase Complete Response(CR) | 37 Participants |
| PLACEBO | Number of Participants With Delayed Phase Complete Response(CR) | 13 Participants |
| APD403 10MG | Number of Participants With Delayed Phase Complete Response(CR) | 27 Participants |
| ADP421 20MG | Number of Participants With Delayed Phase Complete Response(CR) | 21 Participants |
| APD421 40MG | Number of Participants With Delayed Phase Complete Response(CR) | 20 Participants |
p-value: 0.004Regression, Logistic
p-value: 0.0987Regression, Logistic
p-value: 0.1041Regression, Logistic
Secondary
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)
Time frame: 0 to 120 hours after the initiation of chemotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Participants With CR in the Overall Phase. | 33 Participants |
| PLACEBO | Number of Participants With CR in the Overall Phase. | 11 Participants |
| APD403 10MG | Number of Participants With CR in the Overall Phase. | 21 Participants |
| ADP421 20MG | Number of Participants With CR in the Overall Phase. | 17 Participants |
| APD421 40MG | Number of Participants With CR in the Overall Phase. | 17 Participants |
p-value: 0.0235Chi-squared, Corrected
p-value: 0.1651Chi-squared, Corrected
p-value: 0.1332Chi-squared, Corrected