A Phase I, Randomized, Single-Center Study to Investigate the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Profiles of Single and Multiple Doses of R924548 in Healthy Human Subjects

A Phase I, Randomized, Single-Center Study to Investigate the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Profiles of Single and Multiple Doses of R924548 in Healthy Human Subjects - R924548 SAD/MAD study

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON37424

Enrollment

Registered

2011-09-26

Start date

2011-10-31

Completion date

Unknown

Last updated

2024-04-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

immune-mediated diseases rheuma

Interventions

Study Medication Active substance: R548 Activity: janus kinase 1 (JAK1) and janus kinase 3 (JAK3) Dosage form: aqueous suspension or aqueous solution Treatments Part A (SAD) Group A1: a single oral

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Part A, B and D: Healthy male volunteers 18-55 years of age BMI 19.0-31.0 kg/m2;Part C: Healthy male 18-55 years of age Healthy post-menopausal/surgically sterile female volunteers 18-65 years of age BMI 19.0-31.0 kg/m2

Exclusion criteria

Exclusion criteria: Suffering from: hepatitis B, cancer or HIV/AIDS. Participation in another drug study within 3 months before the start of this study. Blood donation within 3 months from the start of this study or in case you have donated more than 1.5 liters of blood (for men) / more than 1.0 liters of blood (for women) in the 10 months before the start of this study.

Design outcomes

Primary

Measure	Time frame
Criteria for evaluation Safety and tolerability: adverse events, vital signs, ECG-parameters, laboratory parameters, physical examination Stopping rules: Dosing for any individual subject will be stopped if the subject experiences a possible Drug-related serious adverse event (SAE) or a possibly Drug-related significant non-serious AE that in the opinion of the Investigator or Sponsors medical representative, warrants discontinuation from the Study for that subjects well-being. Progression to the next higher dose level will be stopped if 1 or more subjects experience a possible Drug-related SAE or a possible Drug-related significant non-serious AE that, in the opinion of the Investigator or Sponsors medical representative, warrants discontinuation of dose escalation or stopping the Study. In Groups A1-A4 only, if S370 (the Ames positive metabolite isolated in dog feces) is found in any subjects feces at an amount 3.6 mg, then escalation to the next dosing group will only occur following approval by the Investigator , Sponsors medical representative and the EC.	—

Measure

Time frame

Criteria for evaluation Safety and tolerability: adverse events, vital signs, ECG-parameters, laboratory parameters, physical examination Stopping rules: Dosing for any individual subject will be stopped if the subject experiences a possible Drug-related serious adverse event (SAE) or a possibly Drug-related significant non-serious AE that in the opinion of the Investigator or Sponsor*s medical representative, warrants discontinuation from the Study for that subject*s well-being. Progression to the next higher dose level will be stopped if 1 or more subjects experience a possible Drug-related SAE or a possible Drug-related significant non-serious AE that, in the opinion of the Investigator or Sponsor*s medical representative, warrants discontinuation of dose escalation or stopping the Study. In Groups A1-A4 only, if S370 (the Ames positive metabolite isolated in dog feces) is found in any subject*s feces at an amount *3.6 mg, then escalation to the next dosing group will only occur following approval by the Investigator , Sponsor*s medical representative and the EC.

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Secondary

Measure	Time frame
Criteria for evaluation Pharmacodynamics: IL-2 stimulated pSTAT5 in blood lymphocytes and GM-CSF stimulated pSTAT5 in granulocytes analysis of blood lymphocyte subsets Pharmacokinetics: plasma R548 and its metabolite R507 and R689 concentrations. metabolite profiling in urine and feces (in Groups A1-A4 only), pharmacokinetic parameters, plasma caffeine and paraxanthine concentrations, pharmacokinetic parameters	—

Measure

Time frame

Criteria for evaluation Pharmacodynamics: IL-2 stimulated pSTAT5 in blood lymphocytes and GM-CSF stimulated pSTAT5 in granulocytes analysis of blood lymphocyte subsets Pharmacokinetics: plasma R548 and its metabolite R507 and R689 concentrations. metabolite profiling in urine and feces (in Groups A1-A4 only), pharmacokinetic parameters, plasma caffeine and paraxanthine concentrations, pharmacokinetic parameters

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)