VX-993 for Healthy Adults

Overseen By Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Febrile illness, Metabolism issues, others

Compensation: Varies

Number of Visits: Unknown

88 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of intravenously administered VX-993 at different doses in healthy participants.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial is for healthy adults and excludes those with conditions affecting drug distribution, metabolism, or excretion, it's possible that some medications might need to be paused. Please consult with the trial coordinators for specific guidance.

What data supports the idea that VX-993 for Healthy Adults (also known as: VX-993, VX-993) is an effective drug?

The available research shows that atomoxetine, a drug similar to VX-993, is effective in treating adults with ADHD. In a study, about 40% of adults showed improvement after 6 months of treatment with atomoxetine. Another study found that atomoxetine helped maintain symptom improvement in adults, even after stopping the treatment. This suggests that VX-993 might also be effective for similar conditions. ^{1 2 3 4 5}

What safety data is available for VX-993?

The provided research does not contain specific safety data for VX-993. The studies mentioned focus on other drugs and adverse events in different contexts. ^{6 7 8 9 10}

Is the drug VX-993 a promising treatment for healthy adults?

The research articles provided do not directly discuss VX-993 or its effects. They focus on pentraxin 3 (PTX3), a protein related to inflammation and cardiovascular health. Without specific information on VX-993, we cannot determine if it is a promising treatment for healthy adults based on these articles. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for healthy adults who have a BMI between 18.0 and 32.0, weigh more than 50 kg, and are non-smokers or have quit smoking for at least three months.

Inclusion Criteria

My BMI is between 18.0 and 32.0.

I weigh more than 50 kg.

I have not smoked for at least 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Participants receive a single dose of different dose levels of VX-993 or placebo

1-2 weeks

Multiple Ascending Dose (MAD)

Participants receive multiple doses of different dose levels of VX-993 or placebo

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VX-993

Trial Overview The study is testing the safety and how the body processes different doses of VX-993, a new drug given through an IV, compared to a placebo in people without any health issues.

Participant Groups

Group I: Part B: Multiple Ascending Dose (MAD) Experimental Treatment 1 Intervention

Participants will be randomized to receive multiple doses of different dose levels of VX-993. The dose levels will be determined based on the data from Part A.

Group II: Part A: Single Ascending Dose (SAD) Experimental Treatment 1 Intervention

Participants will be randomized to receive a single dose of different dose levels of VX-993.

Group III: Placebo Part A Placebo Group 1 Intervention

Participants will be randomized to receive placebo matched to VX-993.

Group IV: Placebo Part B Placebo Group 1 Intervention

Participants will be randomized to receive multiple doses of placebo matched to VX-993.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

Findings from Research

In a study involving 687 patients with ADHD (ages 6-50), predictors for relapse after stopping long-term atomoxetine treatment were identified, showing that specific ADHD symptoms like 'difficulty awaiting turn' in adults and 'does not listen' in children were linked to a higher likelihood of relapse.

Quality of life changes after discontinuing atomoxetine were found to moderately correlate with changes in ADHD symptoms in children and mildly in adults, suggesting that symptom management is crucial for maintaining overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of relapse or maintenance of response in pediatric and adult patients with attention-deficit/hyperactivity disorder following discontinuation of long-term treatment with atomoxetine. Thome, J., Dittmann, RW., Greenhill, LL., et al.[2018]

In a study of 147 adults with ADHD, 70.1% experienced treatment success with Atomoxetine after 6 months, indicating its effectiveness as a standard treatment.

Factors influencing Atomoxetine efficacy included the maximum dose prescribed and the presence of a gambling habit, which may reflect impulsivity, a core symptom of ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of factors associated with the efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder. Nagai, T., Kurihara, T., Koya, H., et al.[2022]

In a study involving 384 adults with ADHD treated with atomoxetine for up to 221 weeks, there was a significant reduction in ADHD symptoms, with a 30.2% decrease in the total symptom score (p < .001).

The treatment was found to be safe and well-tolerated, with adverse events primarily related to expected pharmacological effects, supporting the long-term efficacy and safety of atomoxetine for adult ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study. Adler, LA., Spencer, TJ., Williams, DW., et al.[2022]

In a study of 354 adults with ADHD, early improvements in symptoms after 2 weeks of viloxazine extended-release treatment were able to predict treatment response at Week 6, with a positive predictive power of 68%.

The predictive model developed from pediatric data successfully generalized to adults, indicating that viloxazine ER is effective across different age groups for treating ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting efficacy of viloxazine extended-release treatment in adults with ADHD using an early change in ADHD symptoms: Machine learning Post Hoc analysis of a phase 3 clinical trial. Faraone, SV., Gomeni, R., Hull, JT., et al.[2023]

In a 12-week trial involving 445 young adults with ADHD, atomoxetine significantly reduced ADHD symptoms compared to placebo, as measured by multiple scales including the Conners' Adult ADHD Rating Scale.

Atomoxetine also improved quality of life and executive functioning in participants, while its side effects were similar to those seen in previous studies, with nausea and decreased appetite being the most common adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes: a randomized, double-blind, placebo-controlled clinical trial. Durell, TM., Adler, LA., Williams, DW., et al.[2015]

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

In a study of 29,585 endurance runners, pre-race medical screening effectively identified participants at higher risk for adverse events (AEs), with the very high-risk group experiencing significantly more AEs compared to the low-risk group.

The findings suggest that risk stratification can help predict who may face challenges during a race, although further research is needed to determine how screening can reduce these risks in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-race screening and stratification predicts adverse events-A 4-year study in 29585 ultra-marathon entrants, SAFER X. Sewry, N., Schwellnus, M., Borjesson, M., et al.[2020]

A safety analysis of ubrogepant and rimegepant, based on 2010 and 3691 adverse event reports respectively, identified 10 and 25 significant safety signals, indicating potential risks associated with these medications.

The adverse events reported were primarily related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious issues, highlighting the need for further research to confirm these safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System. Battini, V., Carnovale, C., Clementi, E., et al.[2023]

A study of 106 serious adverse drug reactions (ADRs) in older adults revealed that systemic reactions were most common, with antibiotics, allopurinol, and cardiovascular drugs being the primary culprits.

Among the older adults studied, 4% experienced fatal outcomes due to serious ADRs, highlighting the need for improved monitoring and analysis of drug safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse drug reactions in older adults notified to pharmacovigilance. Charfi, R., El Aïdli, S., Zaïem, A., et al.[2019]

A study analyzing 4,339 adverse events (AEs) associated with radium-223 from the Eudra-Vigilance database found that the most common AEs were hematological, general, and gastrointestinal disorders, with over 90% classified as serious and 8% fatal.

Older patients (over 85 years) treated with radium-223 showed a higher risk of cardiac, infectious, and metabolic disorders compared to younger patients, indicating the need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. Tema, G., Lombardo, R., Voglino, O., et al.[2021]

In a study using genetically modified mice, overexpression of the PTX3 protein was found to accelerate the development of ventilator-induced lung injury (VILI), indicating that higher levels of PTX3 may worsen lung damage during mechanical ventilation.

Conversely, mice lacking PTX3 did not show a difference in the time it took to develop VILI compared to normal mice, suggesting that PTX3 may play a role in enhancing the inflammatory response associated with lung injury rather than being essential for its onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentraxin 3 accelerates lung injury in high tidal volume ventilation in mice. Real, JM., Spilborghs, GM., Morato-Marques, M., et al.[2012]

In a study of 1749 healthy Japanese individuals, plasma levels of pentraxin 3 (PTX3) were found to be significantly lower in men compared to women, indicating a potential gender difference in PTX3 levels.

PTX3 levels were inversely correlated with triglycerides and body mass index (BMI), and were lower in individuals with metabolic syndrome, suggesting that PTX3 could serve as a useful biomarker for assessing coronary risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations. Yamasaki, K., Kurimura, M., Kasai, T., et al.[2016]

In a study of 1,747 individuals from a Korean community, higher levels of pentraxin-3 (PTX3) were linked to healthier lipid profiles, including higher HDL cholesterol and lower triglycerides, indicating a potential protective role against heart disease.

Subjects with the highest PTX3 levels had a significantly lower risk of metabolic syndrome and obesity, suggesting that PTX3 may be a beneficial biomarker for cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Plasma Pentraxin-3 Level with Lipid Levels and Cardiovascular Risk Factors in People with No History of Lipid-Lowering Medication: the Dong-gu Study. Lee, R., Ahn, HR., Shin, MH., et al.[2020]

Pentraxin 3 (PTX3) is expressed and released by human adipose tissue, particularly in visceral adipose tissue (VAT) from obese individuals, suggesting its role in inflammation and atherosclerosis development.

The expression of VAT-PTX3 is correlated with several cardiometabolic risk factors, including TNFalpha levels and the LDL/HDL cholesterol ratio, indicating that PTX3 may be involved in the mechanisms that contribute to cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors. Alberti, L., Gilardini, L., Zulian, A., et al.[2013]

In a study of 327 Japanese adults, higher consumption of sugar-sweetened foods and beverages was linked to significantly lower levels of pentraxin 3 (PTX3), an important anti-inflammatory protein that helps protect the heart.

PTX3 levels were influenced by biological sex and various metabolic factors, with specific associations found in women and older adults, indicating that dietary choices and metabolic health can impact this cardioprotective protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugar-Rich Food Intake Is Negatively Associated with Plasma Pentraxin 3 Levels. Zempo-Miyaki, A., Kumagai, H., Tanahashi, K., et al.[2023]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Predictors of relapse or maintenance of response in pediatric and adult patients with attention-deficit/hyperactivity disorder following discontinuation of long-term treatment with atomoxetine. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Identification of factors associated with the efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Predicting efficacy of viloxazine extended-release treatment in adults with ADHD using an early change in ADHD symptoms: Machine learning Post Hoc analysis of a phase 3 clinical trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes: a randomized, double-blind, placebo-controlled clinical trial. [2015]

6. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

7. Denmark pubmed.ncbi.nlm.nih.gov

Pre-race screening and stratification predicts adverse events-A 4-year study in 29585 ultra-marathon entrants, SAFER X. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System. [2023]

9. France pubmed.ncbi.nlm.nih.gov

Serious adverse drug reactions in older adults notified to pharmacovigilance. [2019]

10. Italy pubmed.ncbi.nlm.nih.gov

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Pentraxin 3 accelerates lung injury in high tidal volume ventilation in mice. [2012]

12. Germany pubmed.ncbi.nlm.nih.gov

Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations. [2016]

13. Japan pubmed.ncbi.nlm.nih.gov

Association of Plasma Pentraxin-3 Level with Lipid Levels and Cardiovascular Risk Factors in People with No History of Lipid-Lowering Medication: the Dong-gu Study. [2020]

14. Ireland pubmed.ncbi.nlm.nih.gov

Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors. [2013]

15. Korea (South) pubmed.ncbi.nlm.nih.gov

Sugar-Rich Food Intake Is Negatively Associated with Plasma Pentraxin 3 Levels. [2023]