Pharmacokinetic Study of KHK7580 in Healthy Adult Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: 1mg KHK7580; Drug: 3mg KHK7580; Drug: 6mg KHK7580; Drug: 12mg KHK7580; Drug: 6mg KHK7580 for 8days

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose administration of 1mg KHK7580	Drug: 1mg KHK7580; Single oral dose administration of 1mg KHK7580
Experimental: Single dose administration of 3mg KHK7580	Drug: 3mg KHK7580; Single oral dose administration of 3mg KHK7580
Experimental: Single dose administration of 6mg KHK7580	Drug: 6mg KHK7580; Single oral dose administration of 6mg KHK7580
Experimental: Single dose administration of 12mg KHK7580	Drug: 12mg KHK7580; Single oral dose administration of 12mg KHK7580
Experimental: Multiple dose administration of 6mg KHK7580 for 8days	Drug: 6mg KHK7580 for 8days; multiple oral dose administration of 6mg KHK7580 for 8days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.
• Collaborators: Kyowa Hakko Kirin China Pharmaceutical Co., LTD.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Actual): June 17, 2021
• Study Completion (Actual): June 17, 2021

Study Registration Dates

• First Submitted: December 18, 2019
• First Submitted That Met QC Criteria: December 18, 2019
• First Posted (Actual): December 20, 2019

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 5, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 7580-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No