Pharmacokinetic Study of KHK7580 in Healthy Adult Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacokinetic Study of KHK7580 in Healthy Adult Volunteers

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: 1mg KHK7580
* Drug: 3mg KHK7580
* Drug: 6mg KHK7580
* Drug: 12mg KHK7580
* Drug: 6mg KHK7580 for 8days


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Personally submitted written voluntary informed consent to participate in the study; Chinese adult ≥20 and <40 years of age at informed consent; 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: Subjects with present illness requiring treatment; 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; Subjects in whom a clinically significant abnormality in the crystalline lens is noted at a pre-study ophthalmological examination; Subjects with urinary tract lithiasis or its past history; Subjects with convulsive seizure or its past history; 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); Subjects with mental disorder or its past history; Subjects who have alcohol/drug dependence or tested positive for any of the drug abuse test items; Subjects with symptomatic allergy disease; Subjects with drug allergy or its past history; 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 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; Subjects who tested positive for any of the infection test items; 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; 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; 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; 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); 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; 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; Prior exposure to KHK7580; Other conditions unfit for participation in this study at the discretion of the investigator or subinvestigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose administration of 1mg KHK7580<br> | Drug: 1mg KHK7580<br>* Single oral dose administration of 1mg KHK7580<br>|
| Experimental: Single dose administration of 3mg KHK7580<br> | Drug: 3mg KHK7580<br>* Single oral dose administration of 3mg KHK7580<br>|
| Experimental: Single dose administration of 6mg KHK7580<br> | Drug: 6mg KHK7580<br>* Single oral dose administration of 6mg KHK7580<br>|
| Experimental: Single dose administration of 12mg KHK7580<br> | Drug: 12mg KHK7580<br>* Single oral dose administration of 12mg KHK7580<br>|
| Experimental: Multiple dose administration of 6mg KHK7580 for 8days<br> | Drug: 6mg KHK7580 for 8days<br>* multiple oral dose administration of 6mg KHK7580 for 8days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) |  | Dosing to study completion | 
| 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 |