Study to Assess Bioequivalence and Adhesion Properties Between Two Granisetron Transdermal Patches.

NCT05027646 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 392MD/48/C
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to evaluate the BE and adhesion properties of granisetron transdermal patches manufactured at 2 different sites. The study has been designed in accordance with the FDA Guidance for Industry. Bioequivalence will be based on the Cmax and AUC to determine the peak and total drug exposure, respectively.

Conditions

Healthy Volunteers

Keywords

Patch; Nausea; Anti-emetic; Granisetron

Outcome Measures

Primary Outcomes (8)

• Area under the plasma concentration versus time curve AUC (0-t)

  AUC from time 0 to the time of the last measurable plasma concentration, calculated using the linear trapezoidal rule

  6 months

• Area under the plasma concentration versus time curve AUC (0-inf)

  AUC from time 0 extrapolated to infinity, calculated as (AUC 0-t + \[Clast/λz\]) where Clast is the last measurable plasma concentration

  6 months

• Peak Plasma Concentration (Cmax)

  Maximum concentration after dosing

  6 months

• Maximum concentration (Tmax)

  Time to reach the maximum plasma concentration after dosing (Tmax)

  6 months

• T1/2

  Terminal phase half-life

  6 months

• CL/F

  Total clearance after dosing

  6 months

• Vz/F

  Apparent volume of distribution during the terminal phase, calculated as (CL/F)λz

  6 months

• Mean adhesion score (FDA scale)

  Adhesion of the patch to the skin is assessed by the FDA 0-4 scoring system. The scoring for adhesion is: 0 = ≥ 90% adhered (essentially no lift off the skin), 1 = ≥ 75% to \< 90% adhered (some edges only lifting off the skin), 2 = ≥ 50% to \< 75% adhered (less than half of the patch lifting off the skin), 3 = \> 0% to \< 50% adhered but not detached (more than half of the patch lifting off the skin without falling off), and 4 = 0% adhered (patched completely off the skin). Adhesion is assessed daily when patches are insitu. The mean adhesion score will be derived from its individual adhesion scores at each assessment time point, averaged across all the equally spaced time points (except baseline timepoint). Difference in mean adhesion score between test and reference transdermal patches will be compared using a mixed-model analysis of variance.

  6 months

Secondary Outcomes (2)

• Number of subjects with treatment related adverse events will be as assessed as mild, moderate or severe and will be summarized descriptively and presented as frequency and percentage.

  6 Months

• Adhesion performance score (FDA Scale)

  6 Months

Study Arms (2)

Part 1 - Bioequivalence

EXPERIMENTAL

Bioequivalence will be measured in approximately 42 healthy male and female subjects at a single center in the US to achieve at least 33 completers.

Drug: Sancuso - Part 1

Part 2 - Adhesion

EXPERIMENTAL

Adhesion will be measured in approximately 90 healthy male and female subjects are planned to be enrolled at a single center in the US.

Drug: Sancuso - Part 2

Interventions

Sancuso - Part 1 DRUG

Part 1 - A Potent anti-emetic and highly selective antagonist of 5-HT3 receptors.

Also known as: Granisetron Transdermal Patch

Part 1 - Bioequivalence

Sancuso - Part 2 DRUG

Part 2 - A Potent anti-emetic and highly selective antagonist of 5-HT3 receptors.

Also known as: Granisetron Transdermal Patch

Part 2 - Adhesion

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female 18 to 55 years, inclusive
• BMI 18 to 30 kg/m2
• Healthy volunteers, health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results and physical examination.
• Agrees to comply with all protocol requirements.
• Able to provide written and voluntary informed consent.
• Female participants of childbearing potential have a negative pregnancy test and agree to adhere to an acceptable methods of birth control.
• Male participants with female partners of childbearing potential agree to acceptable methods of birth control.

You may not qualify if:

• Participant to be excluded if,
• Presents with baseline systolic blood pressure \>140 mm Hg and diastolic blood pressure \>90 mm Hg.
• Any clinically significant ECG finding or QTcF interval \>450 msec for males and \>470 msec for females.
• A history of sensitivity to granisetron or other components of the transdermal patch.
• Pregnant or breastfeeding.
• Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results, as determined by the investigator.
• Participants with following pre-existing liver functioning test elevations will be excluded: alanine aminotransferase or aspartate aminotransferase elevation \>2 × ULN, and/or bilirubin \>2 × ULN
• Acute or chronic renal or hepatic impairment, that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results, as determined by the investigator.
• Acute or chronic psychiatric condition, including, but not limited to compulsive-depressive disorders, anxiety, and/or sleep disorders that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results.
• A history of coronary heart disease, arterial or pulmonary hypertension, supraventricular or ventricular tachycardias, or other arrhythmias or heart rhythm and conduction disorders.
• A positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV types 1 or 2 antibodies at screening.
• If used any prescription (excluding hormonal birth control) or over the counter medications (except paracetamol \[up to 2 g per day\]), including herbal or nutritional supplements, within 14 days before the first application of the transdermal patch.
• If used 5-HT3 receptor antagonists and other serotonergic drugs (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and IV methylene blue) within 14 days before the first application of the transdermal patch.
• If used antihistamines within 72 hours prior to patch application or systemic or topical corticosteroids within 3 weeks before the first application of the transdermal patch.
• Present with a dermatological disorder at any relevant patch application site that precludes proper placement or may interfere with adhesion, site assessment, or potentially affect drug absorption.

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead
• PPD Development, LP: collaborator

Study Sites (1)

PPD Development

Austin, Texas, 78744, United States

Location

Related Publications (2)

• Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs - General Considerations (DHHS 2014). U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). March 2014

  BACKGROUND

• Guidance for Industry: Assessing Adhesion With Transdermal and Topical Delivery Systems for ANDAs (DHHS 2018). U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) October 2018

  BACKGROUND

MeSH Terms

Conditions

Nausea

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-center, randomized, 2-part, open-label, crossover study in healthy subjects to establish BE (Part 1) and evaluate adhesion (Part 2) between granisetron transdermal patches.

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: August 30, 2021
• Study Start: July 6, 2021
• Primary Completion: December 22, 2021
• Study Completion: January 19, 2022
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)