The Safety, Tolerability and Pharmacokinetic Study of HEC68498 in Healthy Male and Female Subjects
Primary Purpose
Idiopathic Pulmonary Fibrosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HEC 68498
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis
Eligibility Criteria
Inclusion Criteria:
- Males or females, of any race, between 18 and 60 years of age, inclusive, at Screening.
- Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
- In good health, determined by no clinically significant findings from medical history,physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is not acceptable) at Screening or Check-in as assessed by the Investigator (or designee).
- Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Section 6.6.
- Where doses exceed 10 mg or where the maximum systemic exposure for any individual subject is predicted to exceed that at the NOAEL of the male rat, male subjects must be sterile. For the purposes of this study, sterile male subjects will include those who have had a vasectomy performed at least 90 days prior to the screening visit and have documentation of azoospermia. Virile male subjects will include all males that do not meet the definition of sterile.
- Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
Exclusion Criteria:
- Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
- Fasting blood glucose >110 mg/dL (confirmed with repeat testing).
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- History of stomach or intestinal surgery or resection, including cholecystectomy, that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
- History of alcoholism or drug/chemical abuse within 2 years prior to Check-in.
- Alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
- Positive urine drug screen (including cotinine) at Screening or Check-in, or positive alcohol breath test at Check-in.
- Positive hepatitis panel and/or positive human immunodeficiency virus test.
- Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing.
- Use or intend to use any prescription or nonprescription medications/products, including St. John抯 wort, vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to dosing,unless deemed acceptable by the Investigator (or designee).
- Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
- Unwilling or unable to abide by the dietary and exercise restrictions .
- Receipt of blood products within 2 months prior to Check-in.
- Donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
- Poor peripheral venous access.
- Have previously completed or withdrawn from this study or any other study investigating HEC68498, and have previously received the investigational product.
- Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
Sites / Locations
- Covance Clinical Research Unit, Inc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
HEC68498
placebo
Arm Description
administered once on first day in each Treatment Period, HEC68498 VS placebo 3:1 ratio
administered once on first day in each Treatment Period
Outcomes
Primary Outcome Measures
Adverse event
To assess the safety and tolerability of single dose administered
Secondary Outcome Measures
AUC0-∞
area under the concentration versus time curve (AUC) from time zero to infinity
AUC0-t
AUC from time zero to the time of the last quantifiable concentration time zero to the time of the last quantifiable concentration
Cmax
maximum observed plasma concentration
tmax
time of the maximum observed plasma concentration
t½
apparent terminal elimination half-life
Vz/F
apparent volume of distribution
Full Information
NCT ID
NCT03502902
First Posted
April 10, 2018
Last Updated
May 5, 2021
Sponsor
Sunshine Lake Pharma Co., Ltd.
Collaborators
Covance
1. Study Identification
Unique Protocol Identification Number
NCT03502902
Brief Title
The Safety, Tolerability and Pharmacokinetic Study of HEC68498 in Healthy Male and Female Subjects
Official Title
A Phase I, Double-blind, Placebo-controlled, Single Oral Dose, Safety, Tolerability, and Pharmacokinetic Study, Incorporating an Evaluation of the Effect of Food on the Pharmacokinetics of HEC68498 in Healthy Male and Female Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
April 26, 2018 (Actual)
Primary Completion Date
March 15, 2019 (Actual)
Study Completion Date
March 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunshine Lake Pharma Co., Ltd.
Collaborators
Covance
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Phase I, Double-blind, Placebo-controlled, Single Oral Dose, Safety, Tolerability, and Pharmacokinetic Study, Incorporating an Evaluation of the Effect of Food on the Pharmacokinetics of HEC68498 in Healthy Male and Female Subjects
Detailed Description
Single-dose, sequential-group design incorporating a food-effect evaluation. Each subject will participate in 1 treatment period, except for Group 5, where each subject will participate in 2 treatment periods. In each group, 6 subjects will receive HEC68498 and 2 subjects will receive placebo. Subjects in Group 5 will receive the same dose level of HEC68498 (or placebo) in both treatment periods. All doses will be administered either after an overnight fast of at least 8 hours or, for subjects in the food-effect evaluation, approximately 30 minutes after starting a standard high-fat breakfast. The first 2 subjects in each group will be dosed (1 subject receiving HEC68498 and 1 subject receiving placebo) 48 hours prior to the remainder of the subjects. There will be a minimum of 7 days between dose escalations. The washout period for subjects in Group 5 will be determined following review of available PK data.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HEC68498
Arm Type
Experimental
Arm Description
administered once on first day in each Treatment Period, HEC68498 VS placebo 3:1 ratio
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
administered once on first day in each Treatment Period
Intervention Type
Drug
Intervention Name(s)
HEC 68498
Intervention Description
HEC68498 is a potent,highly selective inhibitor of class 1 isozymes of phosphoinositide 3-kinase/mammalian(PI3K) and of the mammalian target of rapamycin (mTOR). It has shown good activity against fibrosis and inflammation in vitro and in vivo, with a lower effective dose and better efficacy than pirfenidone and nintedanib.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Adverse event
Description
To assess the safety and tolerability of single dose administered
Time Frame
up to 4 weeks
Secondary Outcome Measure Information:
Title
AUC0-∞
Description
area under the concentration versus time curve (AUC) from time zero to infinity
Time Frame
up to one week
Title
AUC0-t
Description
AUC from time zero to the time of the last quantifiable concentration time zero to the time of the last quantifiable concentration
Time Frame
up to one week
Title
Cmax
Description
maximum observed plasma concentration
Time Frame
up to one week
Title
tmax
Description
time of the maximum observed plasma concentration
Time Frame
up to one week
Title
t½
Description
apparent terminal elimination half-life
Time Frame
up to one week
Title
Vz/F
Description
apparent volume of distribution
Time Frame
up to one week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males or females, of any race, between 18 and 60 years of age, inclusive, at Screening.
Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
In good health, determined by no clinically significant findings from medical history,physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is not acceptable) at Screening or Check-in as assessed by the Investigator (or designee).
Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Section 6.6.
Where doses exceed 10 mg or where the maximum systemic exposure for any individual subject is predicted to exceed that at the NOAEL of the male rat, male subjects must be sterile. For the purposes of this study, sterile male subjects will include those who have had a vasectomy performed at least 90 days prior to the screening visit and have documentation of azoospermia. Virile male subjects will include all males that do not meet the definition of sterile.
Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
Exclusion Criteria:
Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
Fasting blood glucose >110 mg/dL (confirmed with repeat testing).
History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
History of stomach or intestinal surgery or resection, including cholecystectomy, that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
History of alcoholism or drug/chemical abuse within 2 years prior to Check-in.
Alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
Positive urine drug screen (including cotinine) at Screening or Check-in, or positive alcohol breath test at Check-in.
Positive hepatitis panel and/or positive human immunodeficiency virus test.
Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days prior to dosing.
Use or intend to use any prescription or nonprescription medications/products, including St. John抯 wort, vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to dosing,unless deemed acceptable by the Investigator (or designee).
Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
Unwilling or unable to abide by the dietary and exercise restrictions .
Receipt of blood products within 2 months prior to Check-in.
Donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
Poor peripheral venous access.
Have previously completed or withdrawn from this study or any other study investigating HEC68498, and have previously received the investigational product.
Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irene Mirkin, MD
Organizational Affiliation
Covance
Official's Role
Principal Investigator
Facility Information:
Facility Name
Covance Clinical Research Unit, Inc.
City
Daytona Beach
State/Province
Florida
ZIP/Postal Code
32117
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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The Safety, Tolerability and Pharmacokinetic Study of HEC68498 in Healthy Male and Female Subjects
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