- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT01872572
Safety, Tolerability and PK/PD of RB006 in a Healthy Volunteer SAD (SC101)
A Phase 1 Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB006 Administered Subcutaneously, With and Without IV RB007, in Healthy Young Volunteers
This was a Phase 1a, single-center, double-blind, randomized, placebo-controlled study of the safety, tolerability, PK, and PD of single ascending doses of RB006 administered as an SC injection, with and without IV RB007 (an active control agent for RB006), in healthy young volunteers. The study originally planned to enroll 4 cohorts of 8 subjects each (N=32); however, upon review cohort (Cohort 1-A) was necessary in order to fully define the PK profile of SC RB006. Therefore, 36 subjects were enrolled in this study.
Each cohort was balanced by sex with no more than 2/3 of one sex enrolled in any particular cohort (i.e., 5 of 8 subjects in each cohort). No subject participated in >1 dose group, and progression to the next higher dose only occurred if the prior dose level was well tolerated, as assessed by a Safety Review Committee (SRC)
Visão geral do estudo
Status
Condições
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Texas
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Austin, Texas, Estados Unidos, 78744
- PPD Development, LP
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- An Institutional Review Board (IRB)-approved informed consent was signed and dated prior to any study-related activities.
- Subject was between the ages of 18 and 45 years, inclusive.
- Subject was a female with a negative urine or serum pregnancy test or postmenopausal for at least 1 year prior to randomization.
- Subject had a body mass index (BMI) between 18 kg/m2 and 32 kg/m2 (weight/[height]2) and was ≥50 kg and ≤120 kg total body weight.
- Subject had normal (or abnormal and clinically insignificant) laboratory values at Screening.
- Subject was medically normal with no significant abnormal findings at the Screening physical examination.
- Subject had the ability to understand the requirements of the study and a willingness to comply with all study procedures.
- Subject had not consumed and agreed to abstain from taking any dietary supplements or nonprescription drugs
- Subject had not consumed and agreed to abstain from taking any prescription drugs
- Subject had not consumed alcohol-containing beverages for 3 days prior to CRU admission
- Subject had not consumed grapefruit or grapefruit juice within the 14 days prior to CRU admission
- Subject had not used tobacco or nicotine-containing products within 6 months prior to CRU admission
Exclusion Criteria:
- Evidence or history of clinically significant oncologic, pulmonary, hepatic, gastrointestinal (GI), cardiovascular, hematologic, metabolic, neurological, immunologic, nephrologic, endocrine, or psychiatric disease.
- Any evidence or history of intracranial bleeding, aneurysm, or thrombotic or hemorrhagic stroke.
- Any known individual or family history of a bleeding diathesis or coagulopathy.
- Active or expected menstruation during the Treatment Phase (females only).
- History of thrombocytopenia associated with abnormal bleeding or risk of a bleeding event, or screening or baseline platelet count <100,000/mm3.
- History of thrombocytosis associated with a thrombotic event or risk for a thrombotic event, or screening or baseline platelet count >600,000/mm3.
- Endoscopically confirmed peptic ulcer disease within 3 years of CRU admission or GI bleeding within 3 months of CRU admission, including a positive stool for occult blood at Screening or Baseline.
- Urinary tract bleeding within 3 months of CRU admission, including microscopic hematuria on screening or baseline urinalysis.
- Unusual or prolonged bleeding (e.g., gum bleeding, nosebleeds, easy bruising), as documented on the Self-Reported Bleeding Questionnaire, at Screening.
- Severe trauma, fracture, major surgery, or biopsy of a parenchymal organ within 3 months of CRU admission.
- Severe persistent hypertension (systolic pressure >180 mmHg or diastolic pressure >110 mmHg).
- Baseline hemoglobin <12.0 g/dL for males or <11.0 g/dL for females; prothrombin time (PT) greater than the ULN; or aPTT greater than the ULN.
- Clinically significant liver dysfunction (e.g., as evidenced by elevated liver function tests).
- Clinically significant renal dysfunction (e.g., estimated glomerular filtration rate <60 mL/min or serum creatinine >1.5 mg/dL).
- History of illicit drug abuse in the past year or current evidence of such abuse in the opinion of the Investigator.
- Positive findings on urine drug screen.
- Positive findings for human immunodeficiency virus, hepatitis B, and/or hepatitis C at Screening.
- Pregnant or lactating.
- Acute illness within 1 week of CRU admission.
- A history of alcohol abuse in the past year relative to CRU admission.
- Donated plasma within 7 days of study drug administration.
- Donated 1 or more pints of blood (or equivalent blood loss) within 6 weeks prior to study drug administration.
- Use of an investigational drug within 30 days prior to CRU admission or prior REG1 Anticoagulation System exposure.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Outro: Cohort 1
Cohort 1: 6 subjects received Subcutaneous RB006 0.5 mg/kg and 2 subjects received SC placebo
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Placebo
Outros nomes:
Subcutaneous RB006 0.5 mg/kg
Outros nomes:
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Outro: Cohort 1-A
Cohort 1-A: 4 subjects received open-label Subcutaneous RB006 0.5 mg/kg
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Subcutaneous RB006 0.5 mg/kg
Outros nomes:
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Outro: Cohort 2
Cohort 2: 6 subjects received Subcutaneous RB006 1.0 mg/kg and 2 subjects received SC placebo
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Placebo
Outros nomes:
Subcutaneous RB006 1.0 mg/kg
Outros nomes:
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Outro: Cohort 3
Cohort 3: 6 subjects received Subcutaneous RB006 3.0 mg/kg and 2 subjects received SC placebo
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Placebo
Outros nomes:
Subcutaneous RB006 3.0 mg/kg
Outros nomes:
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Outro: Cohort 4
8 subjects received subcutaneous RB006 2.0 mg/kg as well as the following:
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Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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Primary Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Treatment Emergent Adverse Events
Prazo: 10 days
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10 days
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Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
|
Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Serious Adverse Events
Prazo: 10 days
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10 days
|
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Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was pharmacodynamics as determined by change from baseline in aPTT
Prazo: Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216 (and if applicable, 264) hours post RB006 dose
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Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216 (and if applicable, 264) hours post RB006 dose
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Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was pharmacokinetics as determined by Maximum Observed Plasma Concentration (Cmax)
Prazo: Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, and 216 (and if applicable, 264) hours post-RB006 dose
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Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, and 216 (and if applicable, 264) hours post-RB006 dose
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Matthew M Medlock, MD, PPD
Publicações e links úteis
Publicações Gerais
- Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.
- Vavalle JP, Rusconi CP, Zelenkofske S, Wargin WA, Alexander JH, Becker RC. A phase 1 ascending dose study of a subcutaneously administered factor IXa inhibitor and its active control agent. J Thromb Haemost. 2012 Jul;10(7):1303-11. doi: 10.1111/j.1538-7836.2012.04742.x.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Outros números de identificação do estudo
- REG1-CLINSC101
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