Intense pruritus, in oncology subjects, induced by EGFRi MedDRA version: 16.0 Level: LLT Classification code 10023084 Term: Itching System Organ Class: 100000004858
Conditions
Interventions
Product Name: Orvepitant
Pharmaceutical Form: Tablet
INN or Proposed INN: Orvepitant
CAS Number: 579475-24-4
Current Sponsor code: GW823296B
Other descriptive name: GW823296B
Concentration unit: mg mi
Sponsors
NeRRe Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female subjects > 18 years of age • Subjects with a diagnosis of malignant solid tumours and undergoing treatment with one of the following EGFRi medicines [cetuximab (Erbitux®), panitumumab (Vectibix®), erlotinib (Tarceva®), lapatanib (Tyverb®), gefitinib (Iressa®]. Subjects expected treatment duration with their EGFRi must exceed the study duration • Subjects experiencing intense pruritus symptoms following treatment with one of the following EGFRi medicines [cetuximab (Erbitux®), panitumumab (Vectibix®), erlotinib (Tarceva®), lapatanib (Tyverb®), Gefitinib (Iressa®]. Intense pruritus symptoms are defined by subjects reporting a clinic visit NRS score = 7, (where 0 = No Itch and 10 = Worst Itch Imaginable) at the Screening visit, confirmed again at Baseline visit: • Willing to refrain from all non-permitted concomitant medication from the Screening visit through to the Week 8 visit • Willing to refrain from all insomnia medication for the duration of the study • ECOG performance status of 0 to 2 • Life expectancy of > 6 months in the opinion of the Investigator • Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and urine pregnancy test result at Baseline and practice a reliable method of contraception throughout the study. A female is considered of childbearing potential unless she is: o postmenopausal for at least 12 months prior to study drug administration; o without a uterus and/or both ovaries; or o Has been surgically sterile for at least 6 months prior to study drug administration. Reliable methods of contraception are: o Hormonal methods or intrauterine device in use > 90 days prior to study drug administration; o Barrier methods plus spermicide in use at least 14 days prior to study drug administration; or o Vasectomized partner • Female subjects of childbearing potential who are not sexually active may not be required to practice a reliable method of contraception. These subjects may be enrolled at the Investigator's discretion if they commit to remain sexually inactive during the study and understand the possible risks in getting pregnant during the study • Able to understand and comply with the requirements of the study and sign the Informed Consent Form • Laboratory values (Haematology, Biochemistry and Urinalysis values) will be appropriate for subjects with cancer diagnosis, under treatment with EGFRis and dependent on the Investigator’s clinical judgement, where the ranges are not specified below: o Haematology: ? Haemoglobin ? Haematocrit ? Red blood cell (RBC), Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), Mean Corpuscular Haemoglobin Concentration (MCHC) ? White blood cell (WBC) count and differential ? Neutrophils = 1,500 /dL ? Platelets = 100,000 /dL o Biochemistry: ? Serum creatinine = 1.5 mg/dL ? Total bilirubin < 2.0 mg/dL ? Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) = 2.5 x upper limit of normal (ULN) ? Uric acid, total protein, albumin, gamma glutamyl transpeptidase (gamma GT), glucose, phosphorous, potassium, sodium, calcium, and chloride o Urinalysis: ? Dipstick test: protein, blood, ketones, glucose; microscopy will be done on urine samples if the result of the dipstick test for protein or blood is abnormal, but dependent on the site of the subject’s cancer (to be reviewed as n
Exclusion criteria
Exclusion criteria: • Treatment for any other type of pruritus within the previous 3 months (e.g. pruritus in atopic eczema or non-EGFRi-related skin diseases, nephrogenic pruritus, cholestatic pruritus) • Prior use of aprepitant (Emend®) or fosaprepitant (Ivemend®), NK-1 antagonists licensed as antiemetics in cancer therapy within 4 weeks of the Screening visit • History of hypersensitivity or idiosyncratic reaction to any excipients/components of the test medication • Female subjects who are pregnant (positive urine pregnancy test), breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control (except those who are not sexually active) • Prior history of seizure or traumatic brain injury • Subjects with known or suspected brain tumour or metastases • Any current diagnosis or history of a clinically significant abnormality of the neurological system (including demyelinating disorders such as multiple sclerosis, peripheral neuropathic demyelinating or axonal disorders, dementia and other cognitive disorders or significant head injury) • Any moderate to severe acute illness which in the opinion of the Investigator would interfere with the study procedures or study outcome • History of unstable cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases deemed clinically significant by the Investigator, but consistent with diagnosis of solid tumours • History of poor co-operation, non-compliance with medical treatment, or unreliability • Participation in any clinical research study evaluating another investigational drug or therapy within 30 days or at least 5 half-lives (whichever is longer), of the investigational drug prior to consenting to study entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of orvepitant (10 and 30 mg given once daily [od], orally for 4 weeks) compared with placebo in reducing EGFRi-induced intense pruritus ;Secondary Objective: To assess the effects of orvepitant (10 and 30 mg od) compared with placebo on quality of life measures using the Skindex-16 Questionnaire To assess the effects of orvepitant (10 and 30 mg od) compared with placebo on quality of sleep using the Leeds Sleep Evaluation Questionnaire (LSEQ) To assess the safety and tolerability of orvepitant (10 and 30 mg od, orally for 4 weeks) ;Primary end point(s): The primary endpoint will be the change from Baseline of the mean from the last 3 recordings of Week 4 assessed by subject recorded NRS-IVRS. The NRS-IVRS values are recorded in response to the question on the average pruritus intensity. Baseline measurement will be the mean daily NRS-IVRS assessments collected between Screening and the first dose of study medication (prior to first bedtime dose). ;Timepoint(s) of evaluation of this end point: 4 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from Baseline at Weeks 1, 4 and 8 in the Skindex-16 QoL • Change from Baseline at Weeks 1, 4 and 8 in the LSEQ • The change from Baseline of the mean from the last 3 recordings of each week assessed by subject recorded NRS-IVRS • The change from Baseline of the mean of all values for each week assessed by subject recorded NRS-IVRS • The change from Baseline at Weeks 1, 4 and 8 assessed by clinic visit NRS • The VRS at Weeks 1, 4 and 8 • Effect on pruritus intensity of orvepitant (10 and 30 mg) compared with placebo measured using NRS-IVRS as a change from Baseline at each day during Week 1 (Days 2, 3, 4, 5, 6, 7 & 8) • Change from Week 4 to Weeks 5, 6, 7 and 8 assessed by NRS-IVRS and clinic visit NRS (Week 8) • Rescue medication usage, EGFRi dose reductions, and withdrawal from the study due to intense uncontrolled pruritus ;Timepoint(s) of evaluation of this end point: 8 weeks | — |
Countries
Italy, United Kingdom
Contacts
Public ContactPROJECT MANAGEMENT DEPARTMENT
CROMSOURCE SRL
Outcome results
None listed