Pharmacokinetic Study of KHK7580 in Healthy Adult Volunteers

NCT04206657 | Completed Phase 1

• 1 other identifier: 7580-202
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (5)

• 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

Study Arms (5)

Single dose administration of 1mg KHK7580

EXPERIMENTAL

Drug: 1mg KHK7580

Single dose administration of 3mg KHK7580

EXPERIMENTAL

Drug: 3mg KHK7580

Single dose administration of 6mg KHK7580

EXPERIMENTAL

Drug: 6mg KHK7580

Single dose administration of 12mg KHK7580

EXPERIMENTAL

Drug: 12mg KHK7580

Multiple dose administration of 6mg KHK7580 for 8days

EXPERIMENTAL

Drug: 6mg KHK7580 for 8days

Interventions

1mg KHK7580 DRUG

Single oral dose administration of 1mg KHK7580

Single dose administration of 1mg KHK7580

3mg KHK7580 DRUG

Single oral dose administration of 3mg KHK7580

Single dose administration of 3mg KHK7580

6mg KHK7580 DRUG

Single oral dose administration of 6mg KHK7580

Single dose administration of 6mg KHK7580

12mg KHK7580 DRUG

Single oral dose administration of 12mg KHK7580

Single dose administration of 12mg KHK7580

6mg KHK7580 for 8days DRUG

multiple oral dose administration of 6mg KHK7580 for 8days

Multiple dose administration of 6mg KHK7580 for 8days

Eligibility Criteria

• Age: 20 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Kyowa Kirin China Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Beijing hospital

Beijing, Beijing Municipality, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: December 20, 2019
• Study Start: December 20, 2019
• Primary Completion: June 17, 2021
• Study Completion: June 17, 2021
• Last Updated: September 8, 2021

Record last verified: 2021-09

Locations

CN (1)