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

NCT06074757 | Completed Phase 1 DMC

• 1 other identifier: KSHN001034
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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®.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• fluctuation index and pharmacokinetics

  0-28 days

Study Arms (4)

cohort 1

OTHER

Test (25mg) vs RLD (500mg) to assess the safety and tolerability of the test dose

Drug: Fulvestrant injection

cohort 2

EXPERIMENTAL

Test 100 mg

Drug: Fulvestrant injection

cohort 3

EXPERIMENTAL

Test 250 mg

Drug: Fulvestrant injection

cohort 4

EXPERIMENTAL

Test 500mg

Drug: Fulvestrant injection

Interventions

Fulvestrant injection DRUG

phosphate ester of fulvestrant for test arm

Also known as: faslodex

cohort 1; cohort 2; cohort 3; cohort 4

Eligibility Criteria

• Age: 40 Years - 60 Years
• Gender Eligibility Details: healthy female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Kashiv BioSciences, LLC: lead

Study Sites (1)

Triumpharma Cro

Amman, 11941, Jordan

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Dr Uday Harle, Phd medicine

  Kashiv biosciences

  STUDY DIRECTOR

Study Design

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

Model Details: open label, sequential dosing , single ascending dose and multiple dose pharmacokinetic , safety , tolerability study

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: October 10, 2023
• Study Start: March 1, 2023
• Primary Completion: September 10, 2023
• Study Completion: October 1, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

JO (1)