A Phase 1 Study of EXT608 in Healthy Adults

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose safety and tolerability study of EXT608 in healthy subjects. There will be up to 6 sequential dose escalation cohorts of 4 participants. In each cohort 3 participants will receive EXT608 and 1 participant will receive placebo.

Detailed Description
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This is a randomized, double-blind, first-in-human, placebo-controlled single ascending dose study to study the safety, tolerability, PK, and PD of EXT608 in healthy adult participants. Participants will be enrolled into 1 of up to 6 planned single dose cohorts in ascending fashion. Each cohort will consist of 4 participants randomized to receive either EXT608 or placebo, whereby 3 will receive a single injection of EXT608 and 1 will receive matching placebo. Up to 6 dosing cohorts are planned with no single dose escalation to exceed a 3-fold dose increment. A Data Monitoring Board will review the seven-day safety data in each cohort before authorizing the initiation of the next cohort. A screening visit will take place within 28 days of dosing. Eligible participants for each cohort will be admitted to the Clinical Research Unit (CRU) 1 day prior to dosing and remain in the CRU through at least 72 hours after dosing for safety and PK assessments before discharge. The total confinement period will be 4 nights, unless extended for management of AEs at the discretion of the Investigator

Official Title
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EXT608 in Human Healthy Adults; A First-in-Human, Randomized, Double-Blind, Placebo-controlled, Single Dose Escalation Study

Conditions
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Safety Issues

Intervention / Treatment
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* Drug: EXT608
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 18 and 55 years of age. Body mass index between 18.5 and 32 kilogram per square meter (kg/m2), inclusive, with a body weight greater than or equal to (>=) 45 kg. In general good medical health with no clinically significant or relevant abnormalities, A clinical safety laboratory parameter of hemoglobin greater than (>) 11.7 gram per deciliter (g/dl) (females) or 13.1 g/dl (males) and less than (<) 16 g/dl (females) or 17.4 g/dl (males) or, if out of this range, deemed not clinically significant by the Investigator. Total Se-Ca within laboratory normal limits. Serum parathyroid hormone (PTH) concentration within normal laboratory limits. Exclusion Criteria: Evidence of clinically significant (CS) neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious allergy, allergic skin rash, or psychiatric disorder History of drug abuse Currently using any medication (including over-the-counter [OTC], herbal or homeopathic preparations Pregnant, nursing, or planning a pregnancy during the course of or within 3 months of completing this study History of cancer or other malignancy, with the exception of basal cell carcinoma that has been in remission for at least 5 years Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or a human immunodeficiency virus (HIV) ALT and/or AST >1.5 the ULN Increased baseline risk for osteosarcoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Single ascending dose with up to 6 sequential dose escalation cohorts. Participants will be randomized to either study intervention (EXT608) or placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental- EXT608<br>Up to 6 sequential dose escalation cohorts will receive a single dose of EXT608 administered as a subcutaneous injection | Drug: EXT608<br>* EXT608 is an investigational drug administered via subcutaneous injection<br>* Other names: test drug;|
| Placebo Comparator: Placebo comparator<br>Up to 6 participants will receive matching placebo administered as a subcutaneous injection | Other: Placebo<br>* matching placebo administered via subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of EXT608 - Adverse events | Monitoring of treatment-emergent Adverse Events | Day 0 to Day 28 | 
| Safety and tolerability of EXT608-clinical laboratory assessments | Frequency and severity of post-dose change from baseline in hematology, serum chemistry and urinalysis | Day 0 to Day 28 | 
| Safety and tolerability of EXT608- ECG PR interval | Frequency and severity of post-dose change from baseline of 12-lead ECG PR interval | Day 0 to Day 28 | 
| Safety and tolerability of EXT608- ECG QRS interval | Frequency and severity of post-dose change from baseline of 12-lead ECG QRS interval | Day 0 to Day 28 | 
| Safety and tolerability of EXT608- ECG RR interval | Frequency and severity of post-dose change from baseline of 12-lead ECG RR interval | Day 0 to Day 28 | 
| Safety and tolerability of EXT608- ECG QT interval | Frequency and severity of post-dose change from baseline of 12-lead ECG QT interval | Day 0 to Day 28 | 
| Number of participants with participants with treatment-related adverse events as assessed by CTCAE v4.0 - Blood pressure | Frequency and severity of post-dose change from baseline Blood pressure measurement | Day 0 to Day 28 | 
| Number of participants with participants with treatment-related adverse events as assessed by CTCAE v4.0 - Pulse rate | Frequency and severity of post-dose change from baseline Pulse rate measurement | Day 0 to Day 28 | 
| Number of participants with participants with treatment-related adverse events as assessed by CTCAE v4.0 - Respiratory rate | Frequency and severity of post-dose change from baseline Respiratory rate measurement | Day 0 to Day 28 | 
| Safety and tolerability of EXT608 - Physical exam | Physical exam based upon symptoms reported by participant | Day 0 to Day 28 | 
| Safety and tolerability of EXT608- injection site reactions | Percentage of participants with injection site reactions | Day 0 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single dose PK- AUC | Area under the curve | Up to Day 3 | 
| Single dose PK-Cmax | Maximum observed concentration | Up to Day 3 | 
| Single dose PK - Tmax | time to reach maximum observed plasma concentration | up to Day 3 |