Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study
Background: Phase I study to assess the effects of single oral doses of 100, 200, and 300 mg/day of sodium tungstate (OXO-001) in healthy women of childbearing age.Materials and Methods: A randomized, double-blind, dose-finding, and placebo-controlled phase I study was conducted in healthy weight (...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Royan Institute (ACECR), Tehran
2025-04-01
|
| Series: | International Journal of Fertility and Sterility |
| Subjects: | |
| Online Access: | https://www.ijfs.ir/article_714642_a73837043e8772f2a5affde2dfdb81b3.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850185397471019008 |
|---|---|
| author | Agnes Arbat Ignasi Canals Jimena Coimbra Pol Molina-Perelló Marta Llorens Rosa Torres Josep Perello Marta Moral-Blanch Rosa María Antonijoan Joaquim Calaf |
| author_facet | Agnes Arbat Ignasi Canals Jimena Coimbra Pol Molina-Perelló Marta Llorens Rosa Torres Josep Perello Marta Moral-Blanch Rosa María Antonijoan Joaquim Calaf |
| author_sort | Agnes Arbat |
| collection | DOAJ |
| description | Background: Phase I study to assess the effects of single oral doses of 100, 200, and 300 mg/day of sodium tungstate (OXO-001) in healthy women of childbearing age.Materials and Methods: A randomized, double-blind, dose-finding, and placebo-controlled phase I study was conducted in healthy weight (body mass index [BMI] 18.5-24.9 kg/m2) and overweight (BMI 25 to ≥30 kg/m2) volunteers who received OXO-001 or placebo during a menstrual cycle (maximum 28 days). Data recorded were adverse events (AEs), vital signs, electrocardiogram (ECG), laboratory tests, pharmacokinetics (PK) parameters, and transvaginal ultrasound.Results: Thirty women were included in the safety analysis, and 29 completed the study. Thirty-eight treatment emergent adverse events (TEAEs) were reported by 20 participants (15 in the OXO-001 group and 5 in the placebo group). TEAEs were related to OXO-001 administration in 13.2, 10.5, and 15.8% of cases of the 100, 200, and 300 mg doses, respectively. None of the participants discontinued the study, and no serious AEs or deaths were recorded. Differences in TEAEs by BMI were not found. The PK profile showed a fast absorption rate and proportional increases of OXO-001 plasma concentration to increasing doses, suggesting linear PK, with higher concentrations in BMI <25 kg/m2 group higher than in the ≥25 kg/m2 group. There were no relevant changes in vital signs, ECG, ovarian follicle development, endometrial morphology, and laboratory tests before and after the administration of OXO-001 or placebo.Conclusion: The administration of OXO-001 in volunteers of childbearing age was safe and well tolerated, with consistent PK linear profile within doses studied and without detrimental effect on endometrium or ovary-related variables, with similar effects in healthy weight and overweight participants. The maximum studied dose (300 mg/ day) was safe and well tolerated. These data are sufficient to support further clinical trials (registration number: 2016-001276-30). |
| format | Article |
| id | doaj-art-d1cf77d270ca41f4b0e2bf8b56f4da3f |
| institution | OA Journals |
| issn | 2008-076X 2008-0778 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | International Journal of Fertility and Sterility |
| spelling | doaj-art-d1cf77d270ca41f4b0e2bf8b56f4da3f2025-08-20T02:16:45ZengRoyan Institute (ACECR), TehranInternational Journal of Fertility and Sterility2008-076X2008-07782025-04-0119217718510.22074/ijfs.2024.2013704.1554714642Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I StudyAgnes Arbat0Ignasi Canals1Jimena Coimbra2Pol Molina-Perelló3Marta Llorens4Rosa Torres5Josep Perello6Marta Moral-Blanch7Rosa María Antonijoan8Joaquim Calaf9Oxolife, S.L., Barcelona, SpainOxolife, S.L., Barcelona, SpainCenter of Drug Research (CIM), Research Institute of Hospital de la Santa Creu i Sant Pau (IIB-Sant Pau), Barcelona, SpainCenter of Drug Research (CIM), Research Institute of Hospital de la Santa Creu i Sant Pau (IIB-Sant Pau), Barcelona, SpainOxolife, S.L., Barcelona, SpainOxolife, S.L., Barcelona, SpainDepartment of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainOxolife, S.L., Barcelona, SpainClinical Pharmacology Departement, Hospital de la Santa Creu i Sant Pau. Drug Research Center, Institut d’Investigació Biomèdica Sant Pau, Caiber- IIB-Sant Pau. Pharmacology and TherapeuticsDepartment of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainBackground: Phase I study to assess the effects of single oral doses of 100, 200, and 300 mg/day of sodium tungstate (OXO-001) in healthy women of childbearing age.Materials and Methods: A randomized, double-blind, dose-finding, and placebo-controlled phase I study was conducted in healthy weight (body mass index [BMI] 18.5-24.9 kg/m2) and overweight (BMI 25 to ≥30 kg/m2) volunteers who received OXO-001 or placebo during a menstrual cycle (maximum 28 days). Data recorded were adverse events (AEs), vital signs, electrocardiogram (ECG), laboratory tests, pharmacokinetics (PK) parameters, and transvaginal ultrasound.Results: Thirty women were included in the safety analysis, and 29 completed the study. Thirty-eight treatment emergent adverse events (TEAEs) were reported by 20 participants (15 in the OXO-001 group and 5 in the placebo group). TEAEs were related to OXO-001 administration in 13.2, 10.5, and 15.8% of cases of the 100, 200, and 300 mg doses, respectively. None of the participants discontinued the study, and no serious AEs or deaths were recorded. Differences in TEAEs by BMI were not found. The PK profile showed a fast absorption rate and proportional increases of OXO-001 plasma concentration to increasing doses, suggesting linear PK, with higher concentrations in BMI <25 kg/m2 group higher than in the ≥25 kg/m2 group. There were no relevant changes in vital signs, ECG, ovarian follicle development, endometrial morphology, and laboratory tests before and after the administration of OXO-001 or placebo.Conclusion: The administration of OXO-001 in volunteers of childbearing age was safe and well tolerated, with consistent PK linear profile within doses studied and without detrimental effect on endometrium or ovary-related variables, with similar effects in healthy weight and overweight participants. The maximum studied dose (300 mg/ day) was safe and well tolerated. These data are sufficient to support further clinical trials (registration number: 2016-001276-30).https://www.ijfs.ir/article_714642_a73837043e8772f2a5affde2dfdb81b3.pdffertilitypharmacokineticsphase i studysafetysodium tungstate |
| spellingShingle | Agnes Arbat Ignasi Canals Jimena Coimbra Pol Molina-Perelló Marta Llorens Rosa Torres Josep Perello Marta Moral-Blanch Rosa María Antonijoan Joaquim Calaf Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study International Journal of Fertility and Sterility fertility pharmacokinetics phase i study safety sodium tungstate |
| title | Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study |
| title_full | Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study |
| title_fullStr | Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study |
| title_full_unstemmed | Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study |
| title_short | Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study |
| title_sort | safety tolerability and pharmacokinetics of sodium tungstate oxo 001 in healthy female volunteers of childbearing age a randomized double blind dose finding and placebo controlled phase i study |
| topic | fertility pharmacokinetics phase i study safety sodium tungstate |
| url | https://www.ijfs.ir/article_714642_a73837043e8772f2a5affde2dfdb81b3.pdf |
| work_keys_str_mv | AT agnesarbat safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT ignasicanals safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT jimenacoimbra safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT polmolinaperello safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT martallorens safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT rosatorres safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT josepperello safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT martamoralblanch safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT rosamariaantonijoan safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy AT joaquimcalaf safetytolerabilityandpharmacokineticsofsodiumtungstateoxo001inhealthyfemalevolunteersofchildbearingagearandomizeddoubleblinddosefindingandplacebocontrolledphaseistudy |