Trial Outcomes & Findings for A Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting (NCT NCT01376297)

Last Updated: 2014-11-17

Results Overview

This was a safety study where Adverse Events is the primary outcome (defined by the current ICH Guideline for Good Clinical Practice). Patients were randomized according to a 3:1 ratio (netupitant/palonosetron:aprepitant/palonosetron). No formal comparison was planned, the presence of a control in the same patient population helped interpret any unexpected safety finding in the experimental arm.The number of patients was estimated in order to have more than 100 patients treated with the netupitant/palonosetron comination for up to at least six cycles. Based on 100 patients, if a given AE is not observed, an AE incidence of 3% or greater can be excluded with 95% confidence.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

413 participants

Primary outcome timeframe

Participants will be followed for the duration of the chemotherapy, an expected average duration of up to 24 weeks assuming 6 chemotherapy cycles given every 4 weeks

Results posted on

2014-11-17

Participant Flow

A total of 413 patients were randomized (ITT population), 412 patients received study drugs i.e.netupitant/palonosetron combination or aprepitant/palonosetron regimen, both with dexamethasone (safety population)

Participant milestones

Participant milestones
Measure	Netupitant and Palonosetron Plus Dexamethasone Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle Netupitant and Palonosetron Dexamethasone	Aprepitant and Palonosetron Plus Dexamethasone Oral aprepitant hard capsule 125 mg (on Day 1) + 80 mg daily (for the following two days) and oral palonosetron soft capsule 0.50 mg (on Day 1) given with oral dexamethasone at each scheduled chemotherapy cycle. Aprepitant Palonosetron Dexamethasone
Overall Study STARTED	309	104
Overall Study COMPLETED	181	55
Overall Study NOT COMPLETED	128	49

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Netupitant and Palonosetron Plus Dexamethasone n=308 Participants Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle Netupitant and Palonosetron Dexamethasone	Aprepitant and Palonosetron Plus Dexamethasone n=104 Participants Oral aprepitant hard capsule 125 mg (on Day 1) + 80 mg daily (for the following two days) and oral palonosetron soft capsule 0.50 mg (on Day 1) given with oral dexamethasone at each scheduled chemotherapy cycle. Aprepitant Palonosetron Dexamethasone	Total n=412 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 10.44 • n=5 Participants	56.9 years STANDARD_DEVIATION 11.70 • n=7 Participants	56.6 years STANDARD_DEVIATION 10.76 • n=5 Participants
Sex: Female, Male Female	155 Participants n=5 Participants	51 Participants n=7 Participants	206 Participants n=5 Participants
Sex: Female, Male Male	153 Participants n=5 Participants	53 Participants n=7 Participants	206 Participants n=5 Participants
Race/Ethnicity, Customized White	258 participants n=5 Participants	87 participants n=7 Participants	345 participants n=5 Participants
Race/Ethnicity, Customized Black	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	47 participants n=5 Participants	17 participants n=7 Participants	64 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants will be followed for the duration of the chemotherapy, an expected average duration of up to 24 weeks assuming 6 chemotherapy cycles given every 4 weeks

Population: Safety Population

Outcome measures

Outcome measures
Measure	Netupitant and Palonosetron Plus Dexamethasone n=308 Participants Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle Netupitant and Palonosetron Dexamethasone	Aprepitant and Palonosetron Plus Dexamethasone n=104 Participants Oral aprepitant hard capsule 125 mg (on Day 1) + 80 mg daily (for the following two days) and oral palonosetron soft capsule 0.50 mg (on Day 1) given with oral dexamethasone at each scheduled chemotherapy cycle. Aprepitant Palonosetron Dexamethasone
Percentage of Patients With Adverse Events	86.0 percentage of patients with TEAE	91.3 percentage of patients with TEAE

Adverse Events

Netupitant and Palonosetron Plus Dexamethasone

Serious events: 50 serious events

Other events: 265 other events

Deaths: 0 deaths

Aprepitant and Palonosetron Plus Dexamethasone

Serious events: 19 serious events

Other events: 95 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Development

Helsinn Healthcare SA

Phone: +41 91 9852121

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor and investigator(s) agree that no publications discussing trials' results will occur until release of final report. Sponsor has no objections if the investigators publish study results, however the investigator is requested to contact the sponsor before publishing, to prevent premature disclosure of data and is not intended as a restrictive measure concerning results or opinions of investigators.
Publication restrictions are in place

Restriction type: OTHER

Measure	Netupitant and Palonosetron Plus Dexamethasone n=308 participants at risk Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle Netupitant and Palonosetron Dexamethasone	Aprepitant and Palonosetron Plus Dexamethasone n=104 participants at risk Oral aprepitant hard capsule 125 mg (on Day 1) + 80 mg daily (for the following two days) and oral palonosetron soft capsule 0.50 mg (on Day 1) given with oral dexamethasone at each scheduled chemotherapy cycle. Aprepitant Palonosetron Dexamethasone
Blood and lymphatic system disorders Anaemia	18.8% 58/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	25.0% 26/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Blood and lymphatic system disorders Leukopenia	17.9% 55/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	17.3% 18/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Blood and lymphatic system disorders Neutropenia	30.8% 95/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	27.9% 29/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Blood and lymphatic system disorders Thrombocytopenia	12.3% 38/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	15.4% 16/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Gastrointestinal disorders Constipation	8.4% 26/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	8.7% 9/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Gastrointestinal disorders Diarrhoea	10.4% 32/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	18.3% 19/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Gastrointestinal disorders Dyspepsia	5.2% 16/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	2.9% 3/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Gastrointestinal disorders Nausea	5.8% 18/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	10.6% 11/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Gastrointestinal disorders Stomatitis	2.9% 9/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	5.8% 6/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
General disorders Asthenia	9.7% 30/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	11.5% 12/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
General disorders Fatigue	9.4% 29/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	14.4% 15/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
General disorders Pyrexia	6.2% 19/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	9.6% 10/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Investigations Blood creatinine increased	1.9% 6/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	5.8% 6/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Investigations Neutrophil count decreased	5.5% 17/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	3.8% 4/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Metabolism and nutrition disorders Decreased appetite	6.5% 20/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	6.7% 7/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Metabolism and nutrition disorders Hypokalaemia	5.2% 16/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	3.8% 4/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Nervous system disorders Headache	4.9% 15/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	6.7% 7/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Respiratory, thoracic and mediastinal disorders Cough	4.5% 14/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	7.7% 8/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'
Skin and subcutaneous tissue disorders Alopecia	25.0% 77/308 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'	30.8% 32/104 • The reporting period for AEs was the period starting from the time of informed consent signature until 21 (+2) days post study drug administration (Day 1 of last cycle). Based on the medical judgment of the investigator, all non resolved, non serious AEs beyond this date could have been followed for an additional 14 days. At the end of this additional follow up period, all unresolved AEs were documented on the eCRF as 'ongoing.'