SAD Study to Evaluate Safety, Tolerability, and Pharmacokinetic Profile of KSHN001126 in Healthy Post-Menopausal Females

Healthy Postmenopausal Women Clinical Trial

Official title:

An Open-label, Sequential Dosing, Single Ascending Dose (SAD) Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of KSHN001126 in Healthy Human Post-Menopausal Female Volunteers

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06467201
• Other study ID #: CE-24-02
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: March 2025

Study information

• Verified date: June 2024
• Source: Shivanka Research, LLC
• Contact: Ganesh Sangle
• Phone: +91 91684 33399
• Email: ganesh.sangle[@]kashivindia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an Open-label, Sequential dosing, Single Ascending Dose (SAD) Study to Determine the Safety, Tolerability, and Pharmacokinetic (PK) Profile of KSHN001126 in Healthy Human Post-Menopausal Female Volunteers. The primary objective of the study is to evaluate the safety and tolerability of increasing single doses of KSHN001126 while the secondary objective is to evaluate the plasma PK profile of KSHN001126 and its metabolites (KSHN001167, KSHN001168 and Fulvestrant) following ascending single oral doses of KSHN001126.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Able to provide written Informed Consent and communicate with the investigator and comprehend study-related procedures.

2. Healthy, postmenopausal females aged 45 to 60 years old (inclusive), as determined by medical history and physical examination.

3. Body Mass Index at screening between 18 and 30 kg/m2, inclusive.

4. Post-menopausal females (Menopause is defined as the female is either 12 months off menstrual period after the age of 50 years, or 12 months off menstrual period after the age of 40 years and Follicle Stimulating Hormone (FSH) > 40 mIU/mL. Amenorrhea should not be due to lactation).

5. In good general health with no clinically significant illness seen on physical examination or ongoing medical history, as determined by the Investigator.

6. Documented 12-lead ECG with no clinically significant abnormalities (with QTc interval between 360 to 440 msec), as determined by the Investigator in screening or Day 0.

7. No clinically significant abnormalities in screening or Day 0 laboratory tests, as determined by the Investigator (Creatinine clearance should be = 90 mL/min and Blood Urea Nitrogen / AST / ALT / Alkaline phosphatase / Total and direct bilirubin should be < upper limit of normal).

8. Female participants must have a negative serum pregnancy (ß-HCG) test at screening and a negative urine pregnancy test at Day 0 prior to dosing. Female participants must also be non-lactating.

9. The participant is available to volunteer for the entire study duration and is willing to adhere to all protocol requirements.

10. The participant has vital signs at screening, and at check-in within the following ranges:

• Blood Pressure:

• Systolic: (100- 140 mmHg

• Diastolic: (60-90) mmHg

• Body Temperature: (36.1 - 37.8) ºC, Pulse rate: 60 to 100 b/m. Respiratory rate:

12 to 20 bpm

11. Participants with normal findings as determined by gynecological examination and USG Pelvis.

12. With a normal or clinically acceptable mammogram

13. With a normal or clinically acceptable PAP smear test

14. Have a normal chest X-ray (P. A. view).

15. Participant negative for hepatitis B-surface antigen, hepatitis C and Human Immunodeficiency Virus (HIV)

16. Participants who are generally healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring

17. Adequate venous access and can able to give required blood samples.

Exclusion Criteria:

1. The participant is surgically induced postmenopausal female.

2. Pregnant or lactating female participant.

3. Any history of clinically significant cardiac, renal, neurologic, metabolic, pulmonary, gastrointestinal, chronic hepatic disease or any other disease which in the judgment of the Investigator would interfere with the study or confound the study results.

4. History of allergy or major allergic reaction considered to be clinically significant by the Investigator.

5. Receiving or has received any investigational drug within the 30 days before receiving KSHN001126.

6. History or presence of low platelet count, bleeding issues or family history of bleeding disorders.

7. Participant has a history of hypersensitivity to heparin as checked at screening.

8. The participant has known allergy to the drug under investigation, or to any ingredient in the preparation

9. The participant has an evidence of 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.

10. Donated blood within 60 days of screening or otherwise experienced blood loss of >250 mL within the same period.

11. Intending to begin new concomitant drug therapy or over-the-counter medication anytime from screening to the time of administration of study drug.

12. Received or intending to receive a vaccination in the two weeks prior to dosing, or anytime during study participation.

13. Received treatment with a drug that has not received regulatory approval for an indication during the 60 days preceding study enrollment.

14. History of drug and/or alcohol dependence within past 12 months, and/or positive results on drug of abuse or alcohol tests.

15. The participant is a smoker (smoker is defined as reporting tobacco use in the previous 3 months and/or has urine cotinine level equal or more than 500 ng/ml)

16. Has taken any regular, prescribed, or over-the-counter medication with the exception of acetaminophen (maximum 2 g/day) or multi- vitamins in the 2 weeks prior to dosing (other medication may only be taken with the specific approval of the Investigator in consultation with the Medical Monitor).

17. The participant with history of consuming alcohol or caffeine or related xanthine containing foods or beverages such as caffeine in tea, coffee, chocolates, cola and pepsi for 48 hours prior to dosing.

18. The participant has consumed grapefruit-containing beverages and foods 7 days prior to dosing.

19. Malignancy within the last 5 years, with the exception of successfully treated basal cell carcinoma and carcinoma in situ uteri.

20. The participant has prior history of hormonal replacement therapy.

21. The participant has any estrogen- dependent conditions including breast cancer.

22. Any condition that, in the opinion of the investigator, might interfere with study objectives.

23. The participant has a history of osteoporosis or any disease affecting bone or steroid metabolism.

24. Intolerance to/ fear of venipuncture, needles, or blood draws

Related Conditions & MeSH terms

• Healthy Postmenopausal Women

Intervention

Drug:
• KSHN001126 150mg
6 subjects will receive single oral dose of 150 mg
• KSHN001126 300mg
6 subjects will receive single oral dose of 300 mg
• KSHN001126 600mg
6 subjects will receive single oral dose of 600 mg

Locations

Country	Name	City	State
India	Health1 Superspeciality Hospital	Ahmedabad	Gujarat
United States	Advanced Pharma CR	Miami	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Shivanka Research, LLC	Clinexcel Research, Ahmedabad, India, Eric Solutions LLC

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Type, incidence, severity, seriousness, and relatedness of Adverse Events (AEs)	Adverse events reported after dosing will be evaluated	Upto Day 15 after dosing
Primary	Number of participants with abnormal laboratory tests results	Laboratory abnormalities after dosing will be evaluated	Upto Day 15 after dosing
Primary	Number of participants with abnormal vital signs		Upto Day 15 after dosing
Primary	Number of participants with abnormal Electrocardiogram readings	Impact on QTc interval will be evaluated	Upto Day 15 after dosing
Secondary	Evaluate the Peak Plasma Concentration (Cmax) of KSHN001126 and its metabolites (KSHN001167, KSHN001168 and Fulvestrant) following ascending single oral doses of KSHN001126		72 hours after dosing
Secondary	Evaluate the Area under the plasma concentration versus time curve (AUC) of KSHN001126 and its metabolites (KSHN001167, KSHN001168 and Fulvestrant) following ascending single oral doses of KSHN001126		72 hours after dosing
Secondary	Evaluate the Time to maximum concentration (Tmax) of KSHN001126 and its metabolites (KSHN001167, KSHN001168 and Fulvestrant) following ascending single oral doses of KSHN001126		72 hours after dosing
Secondary	Evaluate the half life (T1/2) of KSHN001126 and its metabolites (KSHN001167, KSHN001168 and Fulvestrant) following ascending single oral doses of KSHN001126		72 hours after dosing