Open Label, Sequential Dosing , Single Ascending Dose and Multiple Dose Safety Tolerability and Pharmacokinetic Study

Open Label Sequential Dosing Single Ascending Dose of Four Cohort and Multiple Dose of One Cohort Pharmacokinetics Tolerability and Safety of Fulvestrant Injection as Test Product KSHN001034 vs Reference Product FASLODEX®

The goal of this clinical trial is to learn the comparative pharmacokinetic parameters between the test product and the Reference listed drug in healthy female volunteers

The main question[s] it aims to answer are:

• To assess the sequential dose exposure safety and tolerability of KSHN001034 injection in healthy female subjects after single ascending doses from 25 mg to 500 mg and multiple doses of maximum tolerable dose from single ascending dose
• To assess dose showing comparative bioavailability of KSHN001034 injection in comparison with Faslodex®.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant injection

Detailed Description

Single ascending dose (SAD) of four cohorts (01, 02, 03, and 04) for the test product (25, 100, 250, and 500 mg, respectively).

Subjects who will participate in cohort no. 01 (N= 18 subjects) will be randomized to receive a single dose of the test product 25 mg (N= 10 subjects) or a single dose of the reference product 500 mg (N= 08 subjects). The randomization ratio will be 5:4 for T: R Study Part II: Multiple doses of three treatment arms will be administered in one cohort (N= 32, parallel design).

• Two treatment arms of the test product: T1: the dose lower than maximum tolerated dose (MTD-1) determined in Study Part I, N=12 subjects.

T2: maximum tolerated dose determined in Study Part I, N=12 subjects.

• One treatment arm of the reference product: R: 500 mg, N= 08 subjects The randomization ratio will be 3:3:2 for T1:T2: R]

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Jordan
  • Amman, Jordan, 11941
    • Triumpharma Cro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• The subject is healthy female adult of population aged between 40 to 60 years old (inclusive) at screening.
• The subject has a body weight not less than 50 Kg and according to the BMI range (18.5 - 30 Kg/m2)6 (inclusive) at screening.

• The subject is fully vaccinated for COVID-19 at least two weeks ago, as checked at screening.

  -. The subject is physically and mentally healthy as judged by means of medical and standard laboratory examinations at screening.

• The findings of the subject are within the range of clinical acceptability in medical history, and physical examination, and laboratory results "other than RBC indices (MCH, MCV and MCHC), and hemoglobin, " within "normal ranges" for the laboratory tests performed or abnormalities considered insignificant and justified by the principal/clinical sub- investigator at screening.

• The subject results are within normal range or ± 5% of medical lab reference range for all RBC indices (MCH, MCV and MCHC) and hemoglobin, at screening

  -. The subject's platelets count is within medical lab reference range at screening.

• The subject has a normal ECG (12 leads), including normal QTc (below 440 msec), at screening

  • The subject's chest X-ray, performed within 6 months before screening (if available) or at screening, is normal or considered clinically acceptable with no evidence of ongoing or past serious infections, as per the investigator judgment at screening.
  • The subject vital signs in sitting position are within the following ranges at screening, and on admission day (before admission):

Blood Pressure:

Systolic: (90 - 140) mmHg Diastolic: (60-90) mmHg Body Temperature: (36.1 - 37.2) ºC Pulse rate: 60 to 100 beat per minute. Respiratory rate: 12-18 bpm.

• Kidney function tests (Creatinine, Potassium and Sodium) are within the medical lab reference range and kidney function tests (Blood Urea Nitrogen, and uric acid) are considered clinically acceptable as per the investigator judgment at screening. If creatinine is below the lower normal limit while the other parameters are normal, it will be considered as clinically not significant unless otherwise judged by the investigator.
• Liver function tests (AST, ALT, GGT, and bilirubin (total, direct, and indirect)) results are within the medical lab reference ranges and liver function tests (Alkaline phosphatase, total protein, and albumin) are considered clinically acceptable as per PI / SI judgment at screening.

Exclusion Criteria:

• The subject has an evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of the consent to participation in the study or limit the ability to comply with the protocol requirements, as determined by the principal investigator/clinical Sub-investigator at screening or on admission day (before admission).
• The subject has a known history or presence of any clinically significant abnormality / pathology / disease in any of the body systems, as checked at screening or on admission day (before admission).
• The subject has a clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, active inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), short bowel syndrome, upper gastrointestinal surgery including gastric resection, or other conditions known to interfere with the metabolism or excretion of the drug as determined by the principal investigator/clinical sub-investigator at screening or on admission day (before admission).
• The subject has a history of allergy or major allergic reactions or known allergy/ hypersensitivity to the drug under investigation (Fulvestrant), or to any of the excipients (ethanol, benzyl alcohol, benzyl benzoate, castor oil refined), as checked at screening
• The subject has a history of hypersensitivity to heparin as checked at screening.
• The subject has a history of vaginal bleeding or discharge, bleeding diatheses, thrombocytopenia or taking anticoagulant treatment as checked at screening.
• The subject has symptoms suggestive of COVID-19 as judged by the principal investigator/clinical sub-investigator at screening or admission day (before admission).

The subject is pregnant or nursing (lactating) women, where pregnancy is defined as the state of the female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test at screening or on admission day (before admission).

• The subject has consumed or does not agree to abstain from consuming any beverages or food containing alcohol from screening until donating the last PK sample of the study cohort, as checked at screening or on admission day (before admission).
• The subject does not agree to abstain from consuming any beverages or food containing methylxanthines e.g. caffeine (coffee, tea, cola, energy drinks, chocolate, …etc) for at least 24 hours prior to each dosing and for 24 hrs after each dosing, as checked at screening or on admission day (before admission).
• The subject has taken any prescribed drugs within four weeks preceding first study drug administration or doesn't agree on not taking them until donating last PK sample of the study cohort, as checked at screening or on admission day (before admission).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: cohort 1; Test (25mg) vs RLD (500mg) to assess the safety and tolerability of the test dose	Drug: Fulvestrant injection; phosphate ester of fulvestrant for test arm; Other Names: faslodex
Experimental: cohort 2; Test 100 mg	Drug: Fulvestrant injection; phosphate ester of fulvestrant for test arm; Other Names: faslodex
Experimental: cohort 3; Test 250 mg	Drug: Fulvestrant injection; phosphate ester of fulvestrant for test arm; Other Names: faslodex
Experimental: cohort 4; Test 500mg	Drug: Fulvestrant injection; phosphate ester of fulvestrant for test arm; Other Names: faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability	To assess the dose exposure safety and tolerability of KSHN001034 injection in healthy female subjects after single ascending doses from 25 mg to 500 mg in sequential dosing and multiple doses of maximum tolerable dose from single ascending dose in parallel dosing	0-4 days
bioavailability	To assess dose showing comparative bioavailability of KSHN001034 injection in comparison with Faslodex®.	0-28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fluctuation index and pharmacokinetics	To assess fluctuation index of Test vs RLD in multiple doses and To assess comparative pharmacokinetics of KSHN001034 injection in comparison with Faslodex	0-28 days

Collaborators and Investigators

• Sponsor: Kashiv BioSciences, LLC
• Investigators: Study Director: Dr Uday Harle, Phd medicine, Kashiv biosciences

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): September 10, 2023
• Study Completion (Actual): October 1, 2023

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: October 3, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Actual): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: KSHN001034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No