A Phase I Study of the Co-administration of VLX-1005 and Argatroban in Healthy Human Subjects

NCT05325346 | Completed Phase 1 FDA Drug

• 1 other identifier: VLX-1005-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to characterize the safety and tolerability of VLX-1005 and argatroban administered intravenously, either alone or in combination; and the pharmacokinetics and pharmacodynamics and potential interaction of both agents in a population of healthy subjects.

Conditions

Heparin-induced Thrombocytopenia

Outcome Measures

Primary Outcomes (10)

• Effects of argatroban on Cmax of VLX-1005

  Measure the effects of argatroban on the maximum plasma concentration (Cmax) of VLX-1005

  0 - 51 hours

• Effects of VLX-1005 on Cmax of argatroban

  Measure the effects of VLX-1005 on the maximum plasma concentration (Cmax) of argatroban

  0 - 51 hours

• Effects of argatroban on Tmax of VLX-1005

  Measure the effects of argatroban on the time to maximum plasma concentration (Tmax) of VLX-1005

  0 - 51 hours

• Effects of VLX-1005 on Tmax of argatroban

  Measure the effects of VLX-1005 on the time to maximum plasma concentration (Tmax) of argatroban

  0 - 51 hours

• Effects of argatroban on AUC(inf) of VLX-1005

  Measure the effects of argatroban on the Area Under the Curve \[AUC(inf)\] of VLX-1005

  0 - 51 hours

• Effects of VLX-1005 on AUC(inf) of argatroban

  Measure the effects of VLX-1005 on the Area Under the Curve \[AUC(inf)\] of argatroban

  0 - 51 hours

• Effects of VLX-1005 on whole blood aggregometry

  The change in impedance from baseline by whole blood aggregometry will be measured to assess the effects of VLX-1005 on platelet aggregation

  0 - 9 hours

• Effects of argatroban on whole blood aggregometry

  The change in impedance from baseline by whole blood aggregometry will be measured to assess the effects of argatroban on platelet aggregation

  0 - 9 hours

• Effects of VLX-1005 on PFA-100

  Change in PFA-100 (a platelet pharmacodynamic measure) from baseline, to assess the effects of VLX-1005 on platelet aggregation

  0 - 9 hours

• Effects of argatroban on PFA-100

  Change in PFA-100 (a platelet pharmacodynamic measure) from baseline, to assess the effects of argatroban on platelet aggregation

  0 - 9 hours

Secondary Outcomes (3)

• Safety as measured by incidence of Treatment Emergent Adverse Events

  0 - 30 days

• Effects of VLX-1005 on 12-HETE

  0 - 12 hours

• Effects of argatroban on 12-HETE

  0 - 12 hours

Study Arms (3)

VLX-1005

EXPERIMENTAL

Intravenous administration of VLX-1005 with measurements of PK and PD

Drug: VLX-1005

Argatroban

ACTIVE COMPARATOR

Intravenous administration of argatroban with measurements of PK and PD

Drug: Argatroban

VLX-1005 and Argatroban

OTHER

Intravenous co-administration of VLX-1005 and argatroban with measurements of PK and PD

Drug: VLX-1005; Drug: Argatroban

Interventions

VLX-1005 DRUG

Measurement and comparison of the effects and potential interactions between VLX-1005 and argatroban on safety, tolerability, PK and PD

VLX-1005; VLX-1005 and Argatroban

Argatroban DRUG

Measurement and comparison of the effects and potential interactions between VLX-1005 and argatroban on safety, tolerability, PK and PD

Argatroban; VLX-1005 and Argatroban

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, male or female (non-lactating and not of childbearing potential) subjects age 19 to 55 inclusive.
• Females must have undergone one of the following sterilization procedures at least 6 months prior to the first dosing:
• hysteroscopic sterilization
• bilateral tubal ligation or bilateral salpingectomy
• hysterectomy
• bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status.
• Good general health, with no significant medical history. Subjects must have no clinically significant abnormalities at screening, and/or before administration of the initial dose of study drug.
• Body weight ≥ 50 kg at the screening visit.
• Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive.
• Laboratory values (clinical chemistry and hematology) within the normal reference range. Deviations from this range may be acceptable if they are considered 'not clinically significant' (NCS) by the PI, however, AST and ALT shall be \<1.5x ULN. 7. Males who have not been vasectomized prior to participating in the study must agree to use at least 2 approved methods of contraception, or to abstain from sexual intercourse, from randomization until 90 days after their last dose of VLX-1005 and should refrain from donating sperm during that period. 8. Is a non-smoker and must not have used any nicotine products within three months prior to screening.
• \. Able and willing to attend the necessary visits to the study center.

You may not qualify if:

• Blood donation or recipient of blood transfusion in previous 12 weeks.
• History of clinically significant endocrine, neurological, gastrointestinal, cardiovascular, hematological, hepatobiliary, immunological, renal, respiratory, or genitourinary abnormalities or diseases.
• History of neoplastic disease (with the exception of adequately treated nonmelanomatous skin carcinoma).
• Mentally or legally incapacitated (e.g. has significant emotional problems at the time of Screening Visit or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder within the last 5 years).
• Fever (body temperature \>38 C) or symptomatic viral/bacterial infection or use of antibiotics within 2 weeks prior to Screening.
• Supine resting blood pressure (BP) \>140/90 mmHg or heart rate (HR) \>100 beats per minute at Screening and at Day -2.
• Clinically significant abnormality on ECG performed at the Screening Visit or prior to administration of the initial dose of study drug. (Abnormalities include not being in sinus rhythm, IVCD/BBB or QTcF\>450 ms for males (470 ms for females)).
• Out of range (on repeat) testing for coagulation tests.
• Clinically significant laboratory abnormalities including: Impaired renal function (estimated creatinine clearance (CrCl) of \<80 mL/minute based on CrCl = (140-age \[years\])(body weight \[kg\])/(72)(serum creatinine \[mg/dL\])).
• Positive test for hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody at Screening.
• Participants with a positive toxicology screening panel (urine test including qualitative identification of barbiturates, tetrahydrocannabinol, amphetamines, benzodiazepines, opiates, cocaine, cotinine and ethanol).
• Participants with a history of substance abuse or dependency or history of recreational IV drug use (by self-declaration).13. Participant has a suspected history of alcohol abuse in the 6 months prior to screening.
• \. Use of NSAIDs, aspirin or aspirin-containing medications (and other medications affecting platelet function \[for example cilostazol, clopidogrel, ticagrelor, prasugrel, dipyridamole\]) in the 14 days prior to dosing with study medication. VerifyNow testing will be performed at check-in to exclude possible use of medications that affect platelet function.
• \. Unable to refrain from or anticipates the use of any medications, including prescription and non-prescription drugs and herbal remedies (such as St. John's Wort \[Hypericum perforatum\]), beginning 14 days (or 5 half-lives, whichever is longer) before administration of the initial dose of study drug and continuing throughout the study until the final study visit. There may be certain medications that are permitted at the discretion of the PI and Sponsor (including paracetamol/acetaminophen, medications for the treatment of AEs following administration of study drug).
• \. Subjects who are unlikely to comply with the study protocol or, in the opinion of the PI, would not be a suitable candidate for participation in the study.

Sponsors & Collaborators

• Veralox Therapeutics: lead
• Celerion: collaborator

Study Sites (1)

Celerion, Inc.

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Interventions

argatroban

Study Officials

• Allen Hunt, MBA

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: April 13, 2022
• Study Start: March 7, 2022
• Primary Completion: April 1, 2022
• Study Completion: April 14, 2022
• Last Updated: January 11, 2023

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)