Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers
ApTOLL, a new modulator of Toll-like receptor 4, has demonstrated safety and efficacy in healthy subjects and in stroke patients; however, the route of administration used so far (30 min infusion) can potentially be an issue in the acute stroke units where “time is brain.” To safely reduce the time...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124003226 |
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| author | Macarena Hernández-Jiménez Samuel Martín-Vílchez Gina Mejía-Abril Manuel Roman Sergio Luquero-Bueno David Piñeiro Marc Ribó Francisco Abad-Santos Dolores Ochoa |
| author_facet | Macarena Hernández-Jiménez Samuel Martín-Vílchez Gina Mejía-Abril Manuel Roman Sergio Luquero-Bueno David Piñeiro Marc Ribó Francisco Abad-Santos Dolores Ochoa |
| author_sort | Macarena Hernández-Jiménez |
| collection | DOAJ |
| description | ApTOLL, a new modulator of Toll-like receptor 4, has demonstrated safety and efficacy in healthy subjects and in stroke patients; however, the route of administration used so far (30 min infusion) can potentially be an issue in the acute stroke units where “time is brain.” To safely reduce the time of administration in future clinical trials, a dose-ascending, open-label, phase I clinical trial was conducted in healthy subjects. The objective was to assess the safety and pharmacokinetics of ApTOLL when comparing intravenous infusion (30 min) vs. bolus intravenous injection (1–3 min). The study was divided into three periods: (1) volunteers received 0.1 mg/kg of ApTOLL as a slow intravenous infusion, (2) 0.1 mg/kg of ApTOLL was administered as a single bolus, and (3) subjects received 0.2 mg/kg as a single bolus injection. No adverse events related to ApTOLL administration at any dosing pattern were reported. Maximum concentration was detected at the end of the infusion/injection, and mean half-life was 9.5 h for both routes of administration. These results show that safety and pharmacokinetic profiles were comparable between intravenous infusion and bolus injection of ApTOLL, supporting a change of the route of administration for future clinical practice (ClinicalTrials.gov: NCT05569720). |
| format | Article |
| id | doaj-art-66bd50befa7042889a4a285efed458dd |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-66bd50befa7042889a4a285efed458dd2025-01-17T04:49:28ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102435Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteersMacarena Hernández-Jiménez0Samuel Martín-Vílchez1Gina Mejía-Abril2Manuel Roman3Sergio Luquero-Bueno4David Piñeiro5Marc Ribó6Francisco Abad-Santos7Dolores Ochoa8AptaTargets S.L., Avda. Cardenal Herrera Oria 298, 28035 Madrid, Spain; Neurovascular Research Unit, Pharmacology and Toxicology Department, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain; Corresponding author: Macarena Hernández-Jiménez, AptaTargets S.L., Avda. Cardenal Herrera Oria 298, 28035 Madrid, Spain.Clinical Pharmacology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), 28006 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), 28006 Madrid, SpainAptaTargets S.L., Avda. Cardenal Herrera Oria 298, 28035 Madrid, SpainAptaTargets S.L., Avda. Cardenal Herrera Oria 298, 28035 Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), 28006 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainClinical Pharmacology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), 28006 Madrid, SpainApTOLL, a new modulator of Toll-like receptor 4, has demonstrated safety and efficacy in healthy subjects and in stroke patients; however, the route of administration used so far (30 min infusion) can potentially be an issue in the acute stroke units where “time is brain.” To safely reduce the time of administration in future clinical trials, a dose-ascending, open-label, phase I clinical trial was conducted in healthy subjects. The objective was to assess the safety and pharmacokinetics of ApTOLL when comparing intravenous infusion (30 min) vs. bolus intravenous injection (1–3 min). The study was divided into three periods: (1) volunteers received 0.1 mg/kg of ApTOLL as a slow intravenous infusion, (2) 0.1 mg/kg of ApTOLL was administered as a single bolus, and (3) subjects received 0.2 mg/kg as a single bolus injection. No adverse events related to ApTOLL administration at any dosing pattern were reported. Maximum concentration was detected at the end of the infusion/injection, and mean half-life was 9.5 h for both routes of administration. These results show that safety and pharmacokinetic profiles were comparable between intravenous infusion and bolus injection of ApTOLL, supporting a change of the route of administration for future clinical practice (ClinicalTrials.gov: NCT05569720).http://www.sciencedirect.com/science/article/pii/S2162253124003226MT: Oligonucleotides: Therapies and ApplicationsaptamerTLR4inflammationclinical trialhealthy subjects |
| spellingShingle | Macarena Hernández-Jiménez Samuel Martín-Vílchez Gina Mejía-Abril Manuel Roman Sergio Luquero-Bueno David Piñeiro Marc Ribó Francisco Abad-Santos Dolores Ochoa Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications aptamer TLR4 inflammation clinical trial healthy subjects |
| title | Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers |
| title_full | Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers |
| title_fullStr | Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers |
| title_full_unstemmed | Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers |
| title_short | Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers |
| title_sort | clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of aptoll in healthy volunteers |
| topic | MT: Oligonucleotides: Therapies and Applications aptamer TLR4 inflammation clinical trial healthy subjects |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124003226 |
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