Healthy Volunteer
Conditions
Brief summary
The primary objective is to evaluate the pharmacokinetic profile of KHK7580 in Chinese healthy adult volunteers. The secondary objective is to evaluate its safety and pharmacodynamics.
Interventions
DRUG1mg KHK7580
Single oral dose administration of 1mg KHK7580
DRUG3mg KHK7580
Single oral dose administration of 3mg KHK7580
DRUG6mg KHK7580
Single oral dose administration of 6mg KHK7580
DRUG12mg KHK7580
Single oral dose administration of 12mg KHK7580
DRUG6mg KHK7580 for 8days
multiple oral dose administration of 6mg KHK7580 for 8days
Sponsors
Kyowa Kirin China Pharmaceutical Co., Ltd.
Kyowa Kirin Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
1. Personally submitted written voluntary informed consent to participate in the study; 2. Chinese adult ≥20 and \<40 years of age at informed consent; 3. BMI ≥18.5 kg/m2 and \<25.0 kg/m2 at screening.
Exclusion criteria
Subjects must be excluded from the study if they meet any of the following criteria: 1. Subjects with present illness requiring treatment; 2. Subjects in whom the serum Ca concentration, as measured at pretreatment (screening and Day -1) blood chemistry examination, is below the lower limit of the in-house reference value; 3. Subjects in whom a clinically significant abnormality in the crystalline lens is noted at a pre-study ophthalmological examination; 4. Subjects with urinary tract lithiasis or its past history; 5. Subjects with convulsive seizure or its past history; 6. Subjects with digestive system disorder (peptic ulcer, reflux esophagitis, etc.) or its past history (in this regard, however, a past history of appendicitis is acceptable); 7. Subjects with mental disorder or its past history; 8. Subjects who have alcohol/drug dependence or tested positive for any of the drug abuse test items; 9. Subjects with symptomatic allergy disease; 10. Subjects with drug allergy or its past history; 11. Subjects with a past history or family history of congestive heart failure, hypokalemia, or long QT syndrome; Protocol Number: 7580-202 (ver. 1.2) Date: 25 April, 2019 CONFIDENTIAL 7 12. Subjects in whom a 12-lead ECG tracing before initiation of study drug administration showed, in the judgment of the investigator or subinvestigator, a clinically significant abnormality or an electrocardiographic waveform shape unfit for QT interval measurement; 13. Subjects who tested positive for any of the infection test items; 14. Subjects who have used any drugs (including over-the-counter drugs, external preparations, vitamin preparations, and herbal preparations) within 2 weeks before initiation of study drug administration; 15. Subjects who have smoked a cigarette or used a treatment aid to smoking cessation (including nicotine-containing product chewing/ingestion and nicotine-containing patches) within 2 weeks before initiation of the study drug administration; 16. Subjects who have participated in a clinical study of a drug and practically received the drug within 4 months before initiation of the study drug administration; 17. Subjects who, within 3 months before initiation of the study drug administration, have been hospitalized, undergone surgery, or undergone collection of at least 200 mL of blood (including blood donation and blood component donation); 18. Subjects who did not consent to use an effective contraceptive (e.g., use of condoms) alone or in combination between the day of hospitalization and 3 months after the end of the study drug administration; 19. Pregnant, lactating, possibly pregnant subjects/women (subjects/women of childbearing potential with positive pregnancy test at screening or Day -1, or with negative pregnancy test at screening and Day -1 not using any contraceptive methods), or unwilling to use adequate contraception according to the physician's instructions. Amenorrhea for ≥12 months after the last menstrual period without an alternative medical cause is considered as non-childbearing potential; 20. Prior exposure to KHK7580; 21. Other conditions unfit for participation in this study at the discretion of the investigator or subinvestigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Apparent systemic clearance (CL/F) of KHK7580 | pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of KHK7580 | pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort |
| Maximum Observed Plasma Concentration (Cmax) of KHK7580 | pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort |
| Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t) of KHK7580 | pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of KHK7580 | pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort |
| Plasma Half-Life (t1/2) of KHK7580 | pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort |
| Plasma KHK7580 concentration at each time point | pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort |
Secondary
| Measure | Time frame |
|---|---|
| QTcF | [Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12 |
| QTcB | [Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12 |
| intact PTH level | [Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12 |
| serum P level | [Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12 |
| Incidence of treatment emergent adverse events (TEAEs) | Dosing to study completion |
Countries
China
Outcome results
None listed