scholarly journals Phase 1 healthy volunteer willingness to participate and enrollment preferences

2017 ◽  
Vol 14 (5) ◽  
pp. 537-546 ◽  
Author(s):  
Stephanie C Chen ◽  
Ninet Sinaii ◽  
Gabriella Bedarida ◽  
Mark A Gregorio ◽  
Ezekiel Emanuel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Healthy Volunteers ◽  
Financial Incentives ◽  
Phase 1 ◽  
The United States ◽  
Willingness To Participate ◽  
Invasive Procedures ◽  
Wide Range ◽  
Human Vaccine

Background/aims: Healthy volunteers in phase 1 clinical trials contribute to the development of safe drugs and other biologics and accept risks and burdens without anticipated health benefits from participation. Although emerging data have shown that healthy volunteers are influenced by risk, some still worry that financial incentives lead them to take on unreasonable risk. Yet little is known about healthy volunteers’ preferences and how they make choices about enrolling in research studies. Methods: We surveyed 654 healthy volunteers at the end of their participation in a phase 1 Pfizer trial in the United States, Belgium, and Singapore to examine their reported willingness to enroll in studies of different types, with various procedures, and with possible side-effects. Results: The majority of respondents were willing to join many kinds of studies, but fewer were willing to participate in first-in-human vaccine studies or studies of psychiatric drugs than in other study types. With regard to procedures, a substantial proportion were unwilling to participate in studies that involved invasive procedures, such as a lumbar puncture (45.4%) and bone marrow biopsy (42.3%), but willing to participate in studies with less invasive procedures such as a computed tomography scan of the heart (86.8%), magnetic resonance imaging (87.4%), and skin allergy testing (86.8%). Although there was some variation by gender and region, the majority were willing to participate in studies with side-effects like pain (80%) or nausea and vomiting (64%), but only a minority were willing to join if the research drug would result in their having a one in a million chance of death (34.4%), a small chance of kidney damage (16.7%), or influence how their mind works (23.2%; Figure 4). Conclusion: Our results suggest that healthy volunteers are willing to participate in a wide range of types of phase 1 clinical trials, and express preferences for low risk and familiar studies and study procedures, preferences which are partially affected by offers of payment.

Adverse publicity of serious side effects to healthy volunteers has limited effect on willingness-to-participate in clinical trials

2019 ◽  
Vol 16 (4) ◽  
pp. 440-442
Author(s):  
Nicolas Molinari ◽  
Carey Suehs ◽  
Isabelle Vachier ◽  
Laurie Pahus ◽  
Laurence Halimi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Healthy Volunteers ◽  
Willingness To Participate ◽  
Limited Effect

scholarly journals Foslevodopa/Foscarbidopa Is Well Tolerated and Maintains Stable Levodopa and Carbidopa Exposure Following Subcutaneous Infusion

2021 ◽  
pp. 1-8
Author(s):  
Matthew Rosebraugh ◽  
Wei Liu ◽  
Melina Neenan ◽  
Maurizio F. Facheris
Keyword(s):  
Steady State ◽  
Phase 1 ◽  
The United States ◽  
Therapeutic Window ◽  
Fixed Dose ◽  
Advanced Parkinson’S Disease ◽  
Subcutaneous Infusion ◽  
Study Results ◽  
Wide Range ◽  
Favorable Safety

Background: Foslevodopa/foscarbidopa, formerly known as ABBV-951, is a formulation of levodopa/carbidopa prodrugs with solubility that allows for subcutaneous (SC) infusion and is in development for the treatment of motor complications for patients with advanced Parkinson’s disease (aPD). Objective: The current work characterizes the levodopa (LD) and carbidopa (CD) pharmacokinetics (PK) following SC infusions of foslevodopa/foscarbidopa delivered at four different infusion rates in PD patients. Methods: This was a Phase 1, single ascending dose, single-blind study conducted in 28 adult male and female subjects at seven sites in the United States. Foslevodopa/foscarbidopa was administered via abdominal SC infusion in PD patients over 72 hours. Patients were stratified in 4 groups and received a fixed dose of foslevodopa/foscarbidopa based on their oral daily LD intake. Serial plasma PK samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. Results: LD exposure quickly reached steady state and remained stable with minimal fluctuations. Foslevodopa/foscarbidopa infusion provides stable LD and CD exposures compared to oral LD/CD dosing with the average steady-state exposure ranging from 747-4660 ng/mL for the different groups. Conclusion: Foslevodopa/foscarbidopa was able to provide stable LD and CD exposures in PD patients over 72 hours via SC route of delivery with very low fluctuation in LD concentration level across a wide range of clinically relevant exposures. Foslevodopa/foscarbidopa had a favorable safety profile. The low PK fluctuation following foslevodopa/foscarbidopa infusion is expected to maintain LD exposure to treat aPD patients within a narrow therapeutic window.

scholarly journals Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1885
Author(s):  
Julian S. Rechberger ◽  
Frederic Thiele ◽  
David J. Daniels
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Brain Tumors ◽  
Phase 1 ◽  
Citation Count ◽  
Tumor Therapy ◽  
The United States ◽  
Blood Brain Barrier Disruption ◽  
Current State ◽  
Brain Barrier Disruption

Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.

Phase 1 Clinical Trials of Small Molecules: Evolution and State of the Art

2021 ◽  
Vol 16 ◽  
Author(s):  
John J. Sramek ◽  
Michael F. Murphy ◽  
Sherilyn Adcock ◽  
Jeffrey G. Stark ◽  
Neal R. Cutler
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Healthy Volunteers ◽  
Small Molecules ◽  
Phase 1 ◽  
Dose Range ◽  
Pharmacodynamic Modeling ◽  
Inpatient Setting ◽  
Conducting Phase ◽  
Safe Dose

Background: Phase 1 studies comprise the first exposure of a promising new chemical entity in healthy volunteers or, when appropriate, in patients. To assure a solid foundation for subsequent drug development, this first step must carefully assess the safety and tolerance of a new compound, and often provide some indication of potential effect, so that a safe dose or dose range can be confidently selected for the initial Phase 2 efficacy study in the target patient population. Methods: This review was based on a literature search using both Google Scholar and PubMed, dated back to 1970, using search terms including “healthy volunteers”, “Phase 1”, and “normal volunteers” , and also based on the authors’ own experience conducting Phase 1 clinical trials. This paper reviews the history of Phase 1 studies of small molecules and their rapid evolution, focusing on the critical single and multiple dose studies, their designs, methodology, use of pharmacokinetic and pharmacodynamic modeling, application of potentially helpful biomarkers, study stopping criteria, and novel study designs. Results: We advocate for determining the safe dose range of a new compound by conducting careful dose escalation in a well-staffed inpatient setting, defining the maximally tolerated dose (MTD) by reaching the minimally intolerated dose (MID). The dose immediately below the MID is then defined as the MTD. This is best accomplished by using appropriately screened patients for the target indication, as patients in many CNS indications often tolerate doses differently than healthy non-patients. Biomarkers for safety and pharmacodynamic measures can also assist in further defining a safe and potentially effective dose range for subsequent clinical trial phases. Conclusion: Phase 1 studies can yield critical insights to the pharmacology of a new compound in man and offer perhaps the only development period in which the dose range can be safely and thoroughly explored. Phase 1 studies often contain multiple endpoint objectives, the reconciliation of which can present a dilemma for drug developers and study investigators alike, but which can crucially determine whether a compound can survive to the next step in the drug development process.

Abstract 2009: ALX-0081 a Novel Anti-Thrombotic: Results of a Single-Dose Phase 1 Study in Healthy Volunteers and Further Development in Patients with Stable Angina Undergoing PCI

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jozef Bartunek ◽  
Emanuele Barbato ◽  
Josefin-Beate Holz ◽  
Kristof Vercruysse ◽  
Hans Ulrichts ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Dose Escalation ◽  
Stable Angina ◽  
Thrombus Formation ◽  
Phase 1 ◽  
Controlled Study ◽  
Double Blind ◽  
Phase Ib ◽  
Wide Range

Background : ALX-0081 is a bivalent Nanobody ® based on the variable domain of naturally occurring heavy-chain only antibodies. It binds with high affinity to the A1 domain of von Willebrand Factor (vWF) and thereby blocks the interactions between platelets and vascular collagen. It selectively prevents thrombus formation under high shear stress conditions. Aim : Test ALX-0081 single IV infusions (60 minutes) dosed from 0.5mg to 12mg total in 40 male healthy volunteers in double-blind, randomized, placebo controlled study and assess pharmacokinetic (PK), pharmacodynamic (PD), safety and immunogenicity. Results : ALX-0081 displayed non-linear pharmacokinetic properties, following a 2 compartment model. Ristocetin induced platelet aggregation (RIPA) was analyzed as marker for PD effect with full inhibition (defined as measured levels dropping <10%) observed at ALX-0081 concentrations of ~ 400ng/ml. All subjects dosed ≥ 2mg achieved full RIPA inhibition at 1h post-dosing for maximum of 12h. ALX-0081 treatment was well tolerated and safe, no signs of bleeding were reported and no immunogenic response was detected. Target related mild and transient reductions of vWF and FVIII plasma levels were observed and all events were fully reversible. Phase Ib study design : double-blind, randomized, placebo controlled, multiple ascending dose study. ALX-0081 added to standard anti-thrombotic regimen (ASA, clopidogrel, UFH) in patients with stable angina undergoing elective PCI. Single-dose escalation will be followed by multiple dosing (up to 4 doses in 24h). Dose escalation will be guided by safety and efficacy marker. Endpoints: safety, pharmacological profile, biomarker (RIPA, RICO and ACT) and early clinical outcome (MACE, IMR, molecular marker). Conclusion : ALX-0081 can be administered safely over a wide range of dose-regimen. First results of the phase Ib study in stable angina patients will be presented.

An Investigation into the Therapeutic Action of Hydroxyzine (Atarax) in the Treatment of Nervous Disorders and the Control of the Tobacco-Habit

1958 ◽  
Vol 104 (436) ◽  
pp. 826-833 ◽  
Author(s):  
G. C. Turle
Keyword(s):  
United States ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Side Effects ◽  
Young Children ◽  
Mental Hospital ◽  
The United States ◽  
Child Guidance Clinic ◽  
Therapeutic Action ◽  
Child Guidance

Hydroxyzine hydrochloride (Atarax, UCB 4492) is a tranquillizer which has attracted much interest in the United States, where it has undergone a series of clinical trials with encouraging results. In order to test the claims of American investigators a trial of hydroxyzine was made on a group of psychotic and psychoneurotic patients in a large mental hospital. The effectiveness of hydroxyzine in controlling the tobacco habit was also tested by using volunteer nurses at the hospital. Their observations provided useful information on the subjective action and side effects of the drug. A small number of young children attending a local child guidance clinic were also included in the clinical trial.

scholarly journals Disparity in Clinical Trial Opportunities for Patients with B-Cell Malignancies in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4861-4861
Author(s):  
Sikander Ailawadhi ◽  
Sri Lekha Bodepudi ◽  
Zan Tahir Shareef ◽  
Fabiola Coromoto Cardozo ◽  
Salman Ahmed ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Geographical Distribution ◽  
Research Funding ◽  
Phase 1 ◽  
The United States ◽  
Phase 2 ◽  
B Cell Malignancies ◽  
The Us

Abstract Background: Clinical trials are fundamental to advance therapeutics systematically and improve patient outcomes. Despite this, enrollment on clinical trials remains dismal in the United States (US) and is a constant focus of healthcare policy. We studied distribution of clinical trials for B-cell malignancies over time across the US and unique clinical trial opportunities i.e. individual clinical trials for the given diagnosis at a site that patients may have access to participate. Methods: We abstracted data from clinicaltrials.gov for all trials that had non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) as an inclusion indication between 1999-2018. Clinical trial characteristics and distribution over US geographical divisions (West, Midwest, Northeast, and South) were studied, and differences were assessed by Chi-square test. Results: A total of 1930 trials were identified (NHL: 982, MM: 948), of which 483 were recruiting at the time of data abstraction (NHL: 250, MM: 233). Over the past 2 decades, 182691 patients were enrolled on the various trials (NHL: 81592, MM: 101099). Trials by phase of study included phase 1: 629, phase 1/2: 316, phase 2: 813, phase 2/3: 11 and phase 3: 161. Number of trials by phase separated by NHL and MM are shown in Figure 1. Of these, 197 trials were randomized (NHL: 67, MM: 130). Geographical distribution of trials by diagnosis type is shown in Figure 2. A total of 31806 unique trial opportunities were noted for MM and NHL, of which 9,513 were international and 22,293 were in the US, with a geographical distribution of 5080 in West, 8198 in Midwest, 3944 in Northeast, and 5071 in South. 4,883 of the unique trial opportunities were available at NCI/NCCN accredited sites and 17,410 were at non-NCI/NCCN sites in the US. Treatment characteristics of the trials included monoclonal antibodies in 1218, other targeted agents in 2641, stem cell transplant in 526, and other agents in 517 trials with several trials utilizing more than one of these therapeutic options. There was no statistically significant difference in the distribution of clinical trials by phase of study across various US geographical regions for MM (p=0.71), NHL (p=0.98) or combined MM+NHL (p=0.16). On the other hand, unique trial opportunities were significantly different by study phase and geographical distribution for MM, NHL or MM+NHL (all p<0.001) (Figure 3). Conclusions: Widespread access to clinical trials within a cancer diagnosis is imperative for generalizability of trial results. In a comprehensive, national analysis we noted that while it may appear that clinical trials are available across the US, sites where they are open are distributed unevenly, giving rise to a disparity in access to evidence-based therapeutic advancements for patients. Disclosures Ailawadhi: Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Sher:Affimed: Research Funding.

scholarly journals Landscape of phase 1 clinical trials for minors with cancer in the United States

2020 ◽  
Vol 67 (11) ◽  
Author(s):  
Jaclynne H. Nader ◽  
Dylan V. Neel ◽  
David S. Shulman ◽  
Clement Ma ◽  
Florence Bourgeois ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trials ◽  
Phase 1 ◽  
The United States

Perception and knowledge of clinical trials and factors affecting participation of regional and rural cancer patients of North Queensland

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17558-e17558
Author(s):  
S. S. Sabesan ◽  
B. Burgher ◽  
S. Varma ◽  
P. Piliouras
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Phase 1 ◽  
Willingness To Participate ◽  
Or Education ◽  
Factors Affecting ◽  
Significant Relationships ◽  
Rural Patients ◽  
Phase I And Ii

e17558 Background: The best treatment option for most cancers is participation in clinical trials. Participation in trials is generally low and among rural patients it is likely to be even lower. The aim of this study was to assess knowledge about and attitudes towards clinical trials among rural and regional cancer patients of North Queensland. Methods: A questionnaire-based survey was conducted in outpatient clinics at the Townsville Cancer Centre on all types of cancer patients. Results: The mean age of the 178 participants was 56 years and 45.4% lived in rural or remote areas. Median distance to the trial centre (Townsville) for rural participants was 180 km (range 80 - 1300 km). Being asked whether they would take part in a RCT, 13.2% of participants said no, 56.3% said yes, and 30.5% were unsure. There were no significant relationships between willingness to participate and rurality (p = 0.896) or education level (p = 0.943). For the majority of patients, the number of clinic visits and blood tests required did not matter. Cost of travel (41.1% rural/remote; 23.5% regional; p < 0.001) and the need for family or friends to accompany (38.9% rural/remote; 24.1% regional; p = 0.021) were more important for rural/remote than regional patients as factors affecting participation. Only 16.4% of participants were aware of early studies. After education, percentage of patients willing to participate in phase I and II studies were 57% and 84%, respectively. Rural patients were less willing to participate in phase I studies than regional patients (33.9% vs 52.6%, p = 0.029). Conclusions: Rural patients are as interested in participating in clinical trials as urban patients except for phase 1 trials and should not be excluded because of rurality. Knowledge of trials is poor and there is a need for education early. Cost of travel seems more important for rural patients and as such budgets should include cost of travel to encourage participation of rural patients. No significant financial relationships to disclose.

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