- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT01629446
Lofexidine Mass Balance in Volunteers
A Single-Center, Open-Label, Single-Period, Single-Treatment Study to Determine the Mass Balance of a Single Oral Dose of 14C Labeled Lofexidine
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
The purpose of this study is to determine the mass balance of a single oral dose of 14C labeled lofexidine. Study US WorldMeds Reference Number USWM-LX1-1003, conducted in July and August of 2011, was a single-center, open-label, two-period, two-treatment, randomized sequence study to determine the mass balance and absolute bioavailability of a single oral dose of 14C-labeled lofexidine compared to a single intravenous dose of lofexidine. During the conduct of the study, deficiencies occurred in the collection and processing of urine samples from subjects administered the oral dose of 14C-labeled lofexidine. In study USWM-LX1-1003-1, six male subjects will be dosed with 14C labeled lofexidine oral solution in order to provide accurate data for the mass balance portion of the study. Male subjects who successfully participated in and completed study USWM-LX1-1003 will be enrolled first. Additional male subjects will be enrolled as needed to provide a cohort of 6 subjects. Additional provisions to ensure adequate urine collections have now been implemented at the site and will be utilized in USWM-LX1-1003-1. All blood draws for pharmacokinetic analysis and radioanalysis, and all urine and fecal collection intervals, will occur at the same time points in USWM-LX1-1003-1 as they did in USWM-LX1-1003.
To study the absorption, distribution, metabolism, and elimination (ADME), trace amounts of 14C compounds are quantified using accelerator mass spectrometry (AMS). As a form of an isotope ratio atom counter that achieves the lowest detection limits of any type of mass spectrometry, AMS provides quantitative sensitivity towards 14C labeled compounds to low attomole (10-18) levels. This high degree of sensitivity enables the detection of compounds in very small specimens and/or tissues after administration of doses that can be both chemically and radiochemically small (microdose levels).
At the radioactive dose to be given (approximately 280 nCi; 10.36 kBq) the total radiation exposure to the participant is within the level of background radiation exposure that occurs naturally and orders of magnitude (1000 fold reduction on average) below the levels typical for human metabolism studies using 14C tracers.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Texas
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San Antonio, Texas, Estados Unidos, 78217
- Worldwide Clinical Trials
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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:
- Subject must be a male
- Subject must be between 18 and 50 years of age (inclusive).
- Subject's Body Mass Index (BMI) must be between 18 and 30 kg/m2 (inclusive), and subject must weigh a minimum of 50 kg (110 lbs).
- Subject must voluntarily consent to participate in this study and provide their written informed consent prior to start of any study-specific procedures.
- Subject is willing and able to remain in the study unit for the entire duration of each confinement period.
- Subject's vital signs must be within the following ranges to be included: Vital signs measured sitting after 3 minutes rest; heart rate: 50-90 bpm; systolic BP: 100-140 mmHg; and diastolic BP: 50-90 mmHg. Out-of-range vital signs may be repeated once. Predose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) prior to study drug administration. The Principal Investigator or designee will verify the eligibility of each subject with out-of-range vital signs and document approval prior to dosing.
- Subject is willing to eat entire meals and snacks provided during confinement at the research facility; and understand that the diet will include foods with high fiber content and possibly prune juice.
- Subject is willing to remain in the clinical research center for a minimum of 7 consecutive days during pre-dose, dose, and post-dose evaluation periods.
- Subject is willing to collect all urine and fecal samples for the duration of the study period as required.
- Subject is willing to use a waterless commode located in a designated dry room for urine and feces collection for the duration of the study period as required.
- Subject is willing to abstain from showering for the first 72 to 96 hours following dose administration. After the restriction from showering is lifted, subject must be willing to provide a urine sample prior to showering for the remainder of the confinement period.
Exclusion Criteria:
- History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
- Has a clinically significant abnormal finding on the physical exam, medical history, ECG, or clinical laboratory results at screening.
- History of any syncopal episode or seizures.
- Presence of acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days prior to scheduled dose administration.
- History or presence of allergic or adverse response to lofexidine or related drugs.
- Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.
- Has donated blood or plasma within 30 days prior to the first dose of study medication.
- Has participated in a standard radiolabeled clinical trial within the last 12 months prior to the first dose of study medication or a micro tracer clinical trial within the last 3 months prior to the first dose of study medication.
- Has participated in another clinical trial (randomized subjects only) within 30 days prior to the first dose of study medication.
- Has used any over-the-counter (OTC) medication, including nutritional supplements, within 7 days prior to the first dose of study medication.
- Has used any prescription medication within 14 days prior to the first dose of study medication.
- Has been treated with any known drugs that are moderate or strong inhibitors/inducers of CYP enzymes such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication and that in the Investigator's judgment may impact subject safety or the validity of the study results.
- Has smoked or used tobacco products within 60 days prior to the first dose of study medication.
- Has any prior history of substance abuse or treatment (including alcohol) within the past 2 years.
- Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates).
- Has had a positive test for, or has been treated for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV).
- Has orthostatic hypotension at screening defined as a drop in systolic blood pressure ≥ 20 mmHg or a fall in diastolic blood pressure ≥ 10 mmHg following a 2 minute stand. Out-of-range vital signs may be repeated once. Predose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) prior to study drug administration. The Principal Investigator or designee will verify the eligibility of each subject with out-of-range vital signs and document approval prior to dosing.
- Subjects with a QTcF greater than 450 msec at screening obtained after 5 minutes rest in a supine position using the ECG machine algorithm. The ECGs may be repeated as appropriate in order to confirm values and rule out extraneous results.
- Has irregular bowel habits. ("Irregular" being defined for the purpose of this study as NOT having a bowel movement at least every 2 days.)
- Has been exposed to radiation, including dental or medical imaging such as x ray or tomography, in the 6 months prior to dose administration.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Lofexidine HCl with 14C tracer
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Dose única = Solução contendo 400 μg de lofexidina HCl e uma quantidade traçadora de 14C lofexidina
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Mass Balance
Prazo: plasma, urine, and fecal samples up to 216 hours post dose
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To study the absorption, distribution, metabolism, and elimination (ADME), trace amounts of 14C compounds are quantified using accelerator mass spectrometry (AMS).
As a form of an isotope ratio atom counter that achieves the lowest detection limits of any type of mass spectrometry, AMS provides quantitative sensitivity towards 14C labeled compounds to low attomole (10-18) levels.
This high degree of sensitivity enables the detection of compounds in very small specimens and/or tissues after administration of doses that can be both chemically and radiochemically small (microdose levels).
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plasma, urine, and fecal samples up to 216 hours post dose
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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tolerability of lofexidine oral solution
Prazo: plasma samples over 144 hours post dose
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To determine the tolerability of lofexidine oral solution, plasma samples will be collected over 144s period post dose.
Plasma samples will be collected for possibly pharmacokinetic analysis; radioanalysis samples will be analyzed for combined lofexidine and metabolites using a validated analytical method.
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plasma samples over 144 hours post dose
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Colaboradores e Investigadores
Patrocinador
Colaboradores
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 (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Efeitos Fisiológicos das Drogas
- Agentes Adrenérgicos
- Agentes Neurotransmissores
- Mecanismos Moleculares de Ação Farmacológica
- Anti-hipertensivos
- Agentes do Sistema Nervoso Periférico
- Agentes do Sistema Sensorial
- Agonistas de Receptores Alfa-2 Adrenérgicos
- Alfa-Agonistas Adrenérgicos
- Agonistas Adrenérgicos
- Antagonistas Narcóticos
- Lofexidina
Outros números de identificação do estudo
- USWM-LX1-1003-1
- 1R01DA030916-01 (Número de outro subsídio/financiamento: National Institute on Drug Abuse)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .
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