Pharmacokinetics and Safety of Sancuso and IV Granisetron in Pediatrics Aged 6 to 12 Years

Phase 1

Withdrawn

• Conditions: Chemotherapy Induced Nausea and Vomiting
• Interventions: Drug: Sancuso; Drug: IV granisetron

• Registration Number: NCT01596413
• Lead Sponsor: Kyowa Kirin Pharmaceutical Development Ltd

Brief Summary

The purpose of this study is to determine the dosing strategy for adolescents aged 6 to 12 years.

Detailed Description

This is an open-label, multi-center, cross-over study in male and female pediatric cancer patients, aged 6 to 12 years of age who are receiving at least 2 cycles of emetogenic chemotherapy requiring 5-HT3 antagonist treatment of up to 5 days duration. The study is designed to evaluate the safety and PK of transdermal granisetron (Sancuso® patch) in a pediatric population (aged 6 to 12 years), using a population PK approach.

Study Timeline

• Study First Submitted: 2012-04-26
• Study First Submitted QC: 2012-05-09
• Study First Posted: 2012-05-11
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-25
• Last Update Posted: 2024-07-26

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. 6 to 12 years of age inclusive at screening.

2. Written patient or parental (or appropriate legal representative) IRB approved informed consent as appropriate.

3. Written patient assent (as appropriate).

4. Confirmed malignancy.

5. Scheduled to receive 2 or more cycles* of emetogenic chemotherapy requiring 5-HT3 antagonist treatment.

6. Scheduled to receive one or more consecutive days of 5-HT3 antagonist treatment, per cycle, as CINV prophylaxis.

   • The cycles of chemotherapy must be consecutive (i.e. one followed by the other) but do not have to be the first and second cycle of a line of treatment.

Exclusion Criteria

1. Hypersensitivities, allergies or contraindications to study medications; intolerance of medical tape or sticking plaster.

2. Clinical or laboratory signs and symptoms of significant cerebral, cardiovascular, respiratory, renal, hepatobiliary, pancreatic or infectious disease, which in the Investigator's judgment may interfere with the study assessment or completion of the study.

3. Patients with a known history or predisposition to cardiac conduction interval abnormalities, including QT Syndrome, or known family history of long QT Syndrome or taking medications that are known to prolong the QT interval.

4. Patients scheduled to have routine surgery during the study duration.

5. Patients with a life expectancy of < 6 months.

6. Scarring or significant skin disease on both upper arms.

7. Female patients who are pregnant or breast-feeding. All post menarche female patients must have a pregnancy test at screening.

8. Patients who are known or thought to be sexually active must use effective birth control.**

9. Administration of other investigational drugs within 30 days preceding the screening visit, except for anticancer treatments.

10. Any conditions associated with non-compliance.

    • Effective birth control includes absolute abstinence or double barrier birth control methods i.e. condom and one of the following: combined oral contraceptive, diaphragm, depot contraceptive injection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sancuso Arm	Sancuso	Transdermal Patch 34.3mg graniestron per patch, size 52cm2 Dose: 3.1mg/24 hrs
IV Granisetron	IV granisetron	Aqueous solution for IV administration 1 mg/mL ampoules Dose: 0.01mg/kg (maximum 1 mg)

Primary Outcome Measures

Name	Time	Method
Plasma concentration	Up to 7 days	Analysis of the plasma concentration of Intravenous granisetron vs transdermal granisetron in pediatric patients receiving chemotherapy over two sequential cycles.

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events, application site assessment and clinically significant changes in laboratory assessments over 2 cycles of chemotherapy	From screening until 15 days after the last dose of IV granisetron	Incidence, frequency, and severity of AEs and SAEs, including clinically significant changes in laboratory assessments and application site assessment.
Number of participants with change in ECG parameters	Through study completion, an average of 8 weeks	12 lead ECGs will be conducted to time match PK samples after at least 5 minutes supine rest
Number of participants with change in vital signs	Through study completion, an average of 8 weeks	Change in pulse, systolic and diastolic blood pressures measurements
Number of participants with change in physical assessment including height, weight, BMI and BSA	Through study completion, an average of 8 weeks	Change in height and weight to calculate BMI and BSA