A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of VS 105

NCT03043482 | Completed Phase 1 FDA Drug

• 1 other identifier: VS 105 SAD MAD 001
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the safety, tolerability, and PK following single and multiple ascending dose administration of VS-105 in healthy subjects and patients with chronic kidney disease stage 5D (CKD-5D) on hemodialysis.

Conditions

Chronic-kidney Disease Stage 5D on Stable Hemodialysis

Keywords

VS-105; Renal Insufficiency, Chronic; Secondary hyperparathyroidism

Outcome Measures

Primary Outcomes (6)

• Safety and tolerability of single and multiple ascending doses of VS 105 administered orally to healthy and HD subjects (numbers and percentages of adverse events).

  Adverse events will be counted within each treatment and study part. The numbers and percentages of adverse events will be tabulated by body system, preferred term, and severity.

  3 weeks

• Pharmacokinetic (PK) of VS-105 in serum: area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration

  AUC0-last: The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration.

  pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 and 16 hours and 2, 3, 7, 8, 9, 14, 15, 16 days after dosing.

• PK of VS-105 in serum: area under the serum concentration-time curve from time zero to infinity.

  AUC0-∞: The area under the serum concentration-time curve from time zero to infinity

  pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 and 16 hours and 2, 3, 7, 8, 9, 14, 15, 16 days after dosing.

• PK of VS-105 in serum: observed maximum serum concentration following drug administration

  Cmax: The observed maximum serum concentration following drug administration

  pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 and 16 hours and 2, 3, 7, 8, 9, 14, 15, 16 days after dosing.

• PK of VS-105 in serum: terminal elimination half-life

  T1/2: The terminal elimination half-life

  pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 and 16 hours and 2, 3, 7, 8, 9, 14, 15, 16 days after dosing.

• PK of VS-105 in serum: time to reach the maximum concentration after drug administration

  Tmax: The time to reach the maximum concentration after drug administration

  pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 and 16 hours and 2, 3, 7, 8, 9, 14, 15, 16 days after dosing.

Secondary Outcomes (3)

• Serum calcium (ionized) in healthy and HD subjects

  Pre-dose and 1, 2, 15, 21 days after dosing

• Serum phosphorous in healthy and HD subjects

  Pre-dose and 1, 2, 15, 21 days after dosing

• Serum intact parathyroid hormone (iPTH) in healthy and HD subjects

  Pre-dose and 1, 2, 15, 21 days after dosing

Study Arms (3)

Single VS-105/placebo to healthy

EXPERIMENTAL

Single ascending dose VS-105 or placebo to healthy subjects

Drug: Single VS-105/placebo to healthy

Multiple VS-105/placebo to healthy

EXPERIMENTAL

Multiple ascending dose VS-105 or placebo to healthy subjects

Drug: Multiple VS-105/placebo to healthy

Multiple VS-105/placebo to HD subjects

EXPERIMENTAL

Multiple ascending dose VS-105 or placebo to hemodialysis (HD) subjects

Drug: Multiple VS-105/placebo to HD subjects

Interventions

Single VS-105/placebo to healthy DRUG

In Part 1, single ascending doses of VS-105 or placebo will be administered to approximately 5 cohorts of 8 healthy subjects in each cohort with 6 receiving active and 2 receiving placebo.

Also known as: CK15

Single VS-105/placebo to healthy

Multiple VS-105/placebo to healthy DRUG

In Part 2, multiple ascending doses of VS 105 or placebo will be administered each morning over 7 consecutive days to approximately 3 cohorts of 8 healthy subjects in each cohort with 6 receiving active and 2 receiving placebo..

Also known as: CK15

Multiple VS-105/placebo to healthy

Multiple VS-105/placebo to HD subjects DRUG

In Part 3, multiple ascending doses of VS 105 will be administered over 14 consecutive days to approximately 3 cohorts that will each include 4 hemodialysis subjects with 3 receiving active drug and 1 receiving placebo.

Also known as: CK15

Multiple VS-105/placebo to HD subjects

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Subjects (Parts 1 \& 2)
• Eligible healthy subjects must meet all of the following criteria to quality for enrollment in this study:
• Healthy male and female subjects between 18 and 60 years of age (inclusive). Healthy status, as determined by the investigator, will be based on medical and surgical history, as well as a complete physical examination including vital signs, electrocardiogram (ECG), and laboratory test results.
• A body mass index (BMI) between 18 and 35 kg/m2 (inclusive).
• Female subjects of childbearing potential must be non pregnant and non lactating, and have a negative serum pregnancy test at Screening and a negative serum or urine pregnancy test on Day 1 (if initial serum human chorionic gonadotropin \[hCG\] test results are indeterminate, follow up testing should be performed). Female subjects of childbearing potential (including perimenopausal women who have had menstrual bleeding within 1 year) must be using a method of birth control considered to be appropriate by the investigator (eg, abstinence, double barrier methods, hormonal contraceptives, or partner with vasectomy) for the entire duration of the trial. Female subjects of childbearing potential must agree to use appropriate birth control from the time of Screening until at least 1 month after their last dose of study drug.
• Women are considered to be not of childbearing potential if they are postmenopausal (defined as amenorrheic for ≥12 months with a confirmed follicle stimulating hormone \[FSH\] ≥ 40 mIU/mL) or if they have been surgically sterilized.
• Male subjects must either: remain abstinent from intercourse, be sterile, or agree to use a method of birth control considered to be appropriate by the investigator (eg, condom with spermicide) from the time of Screening until 1 month after their last dose of study drug.
• Non smoker (and no use of other tobacco or nicotine containing products) as documented by history (no nicotine use over the past 6 months) and a negative cotinine test at Screening and Day 1.
• Capable of understanding the written informed consent form (ICF) and providing signed and witnessed written informed consent, as well as willing and able to comply with protocol requirements.
• Hemodialysis Subjects (Part 3)
• Eligible subjects with ESRD requiring HD must meet all of the following criteria to qualify for enrollment in this study:
• Subject has end stage renal disease and is on a stable (defined as Kt/V ≥ 1.2 on two occasions within 3 months of screening) HD regimen (prescribed at least 3 times/week) for at least 3 months prior to screening.
• to 75 years of age (inclusive).
• Serum calcium: 8.0 to 10.0 mg/dL; serum phosphorus: 3.0 to 7.0 mg/dL; and serum iPTH: 200 to 1000 pg/mL (at the time of Screening).
• Subjects who have been receiving other vitamin D receptor analogs (eg, calcitriol, paricalcitol \[Zemplar\], doxercalciferol \[Hectorol\]) must allow for a washout period of 3 weeks prior to study drug administration on Day 1.

You may not qualify if:

• Hemodialysis Subjects (Part 3)
• Subjects undergoing hemodialysis who meet any of the following criteria will be excluded from the study:
• Receiving blood purification therapy other than hemodialysis.
• Dialysis via central venous catheter.
• Expected to undergo pre emptive or scheduled renal transplant within 6 months after Screening.
• Pregnant (positive pregnancy test) or lactating women, and male subjects whose female partners are pregnant or lactating. If serum hCG pregnancy test results are indeterminate, follow up testing should be performed to determine eligibility.
• History of significant gastrointestinal, hepatic, broncho pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis, or any other unstable or new onset medical conditions that, in the opinion of the investigator, would constitute a risk factor for study participation or receipt of study drug.
• ECG heart rate (HR) \<45 bpm or HR \>100 bpm; QTcF \>500 ms.
• History of having received or currently receiving any systemic anti neoplastic (including radiation) or immune modulatory treatment (including systemic oral corticosteroids) ≤ 6 months prior to the first dose of study drug or such treatment is expected to be needed at any time during the study.
• Subjects who have had significant acute infection (eg, influenza, local infection, acute gastrointestinal symptoms) or any other clinically significant illness within 2 weeks prior to the first dose of study drug.
• History of significant gastrointestinal diseases (such as gastric or duodenal ulcers) that affect the absorption of the study drug. Subjects with a history of gastrointestinal disease may be allowed if there is no evidence of active disease for 3 months prior to Day 1 or at the discretion of the investigator.
• Any confirmed significant allergic reactions (anaphylaxis or angioedema) against any drug, or multiple drug allergies (non active hay fever is allowable per the investigator's discretion).
• Any clinically significant concomitant disease or condition (including treatment for such conditions) that could either interfere with or, in the opinion of the investigator, pose an unacceptable risk to the subject.
• Positive test at Screening for Hepatitis B (HBsAg) or human immunodeficiency virus (HIV Ab). If a subject has positive test results for Hepatitis C (HCV RNA or HCVAb) but liver function tests are otherwise not clinically significant, the subject may be included at the investigator's discretion.
• Any other clinically significant abnormalities in laboratory test results at Screening. In the case of uncertain or questionable results, tests performed during Screening may be repeated before the first dose of study drug to confirm eligibility.

Sponsors & Collaborators

• Vidasym, Inc.: lead

Study Sites (1)

DaVita Clinical Research

Lakewood, Colorado, 80228, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Study Officials

• Adam Hardies

  Davita Clinical Research

  STUDY DIRECTOR

• Robert Williams

  Davita Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: February 6, 2017
• Study Start: January 24, 2017
• Primary Completion: March 31, 2018
• Study Completion: March 31, 2018
• Last Updated: October 7, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)