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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KSHN001126 150mg | Experimental | Low Dose |
|
| KSHN001126 300mg | Experimental | Mid Dose |
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| KSHN001126 600mg | Experimental | High Dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KSHN001126 150mg | Drug | 6 subjects will receive single oral dose of 150mg |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Type, incidence, severity, seriousness, and relatedness of Adverse Events (AEs) | Adverse events reported after dosing will be evaluated | Upto Day 15 after dosing |
| Number of participants with abnormal laboratory tests results | Laboratory abnormalities after dosing will be evaluated | Upto Day 15 after dosing |
| Number of participants with abnormal vital signs | Upto Day 15 after dosing | |
| Number of participants with abnormal Electrocardiogram readings | Impact on QTc interval will be evaluated | Upto Day 15 after dosing |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| 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 |
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Inclusion Criteria:
Able to provide written Informed Consent and communicate with the investigator and comprehend study-related procedures.
Healthy, postmenopausal females aged 45 to 60 years old (inclusive), as determined by medical history and physical examination.
Body Mass Index at screening between 18 and 30 kg/m2, inclusive.
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).
In good general health with no clinically significant illness seen on physical examination or ongoing medical history, as determined by the Investigator.
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.
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).
Female participants must have a negative serum pregnancy (β-HCG) test at screening and a negative urine pregnancy test at Day 0 prior to dosing. Female participants must also be non-lactating.
The participant is available to volunteer for the entire study duration and is willing to adhere to all protocol requirements.
The participant has vital signs at screening, and at check-in within the following ranges:
Blood Pressure:
Body Temperature: (36.1 - 37.8) ºC, Pulse rate: 60 to 100 b/m. Respiratory rate: 12 to 20 bpm
Participants with normal findings as determined by gynecological examination and USG Pelvis.
With a normal or clinically acceptable mammogram
With a normal or clinically acceptable PAP smear test
Have a normal chest X-ray (P. A. view).
Participant negative for hepatitis B-surface antigen, hepatitis C and Human Immunodeficiency Virus (HIV)
Participants who are generally healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring
Adequate venous access and can able to give required blood samples.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Advanced Pharma CR | Miami | Florida | 33147 | United States | ||
| Health1 Superspeciality Hospital |
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| KSHN001126 300mg |
| Drug |
6 subjects will receive single oral dose of 300mg |
|
| KSHN001126 600mg | Drug | 6 subjects will receive single oral dose of 600mg |
|
| 72 hours after dosing |
| 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 |
| 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 |
| Ahmedabad |
| Gujarat |
| 380058 |
| India |