A Randomized, Double-Blind, Placebo-Controlled, Active Comparator, Ascending Single and Multiple Dose, Seamless Design Study to Explore the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Two Orally Administered Compounds, ATF936 and AXT914, in Healthy Male and Female Subjects

Novartis1 site in 1 country65 target enrollmentNovember 2006

ConditionsHealthy

InterventionsATF936 AXT914

DrugsATF936 AXT914

Overview

Phase: Phase 1
Intervention: ATF936
Conditions: Healthy
Sponsor: Novartis
Enrollment: 65
Locations: 1
Primary Endpoint: Phase B: A head-to-head comparison of ATF936 and AXT914, each given at its pharmacologically effective dose as determined in Phase A.
Status: Completed
Last Updated: 17 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a first-in-human study and is designed to evaluate the safety, tolerability, pharmacodynamic and pharmacokinetic effects of a single and multiple-doses of ATF936 and AXT914 administered orally in healthy subjects.

Registry

clinicaltrials.gov

Start Date

November 2006

End Date

April 2008

Last Updated

17 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Novartis

Eligibility Criteria

Inclusion Criteria

•Study population:
•Open-label safety cohort, Phases A and B: Healthy male and female subjects between the ages 18 to 68 years (inclusive), in good health as determined by past medical history, physical examination, vital signs assessments, electrocardiograms, routine laboratory testing (hematology, biochemistry, urinalysis) and the opinion of the investigator at screening and baseline. Female subjects must be of non-childbearing potential who are either surgically sterilized or are post-menopausal (see inclusion criterion #2 below)
•Phase C: Healthy post-menopausal females of up to and including 68 years of age, in good health as determined by past medical history, physical examination, vital signs assessments, electrocardiograms, routine laboratory testing (hematology, biochemistry, urinalysis) and the opinion of the investigator at screening and baseline.
•All Phases:
•Post menopausal status is established according to the following guidelines:
•Cessation of menses for ≥ 3 years.
•Documented total hysterectomy/bilateral oophorectomy at least 2 years prior to study participation.
•Cessation of menses for \< 25 years.
•FSH level \> 30 IU/L (confirmed prior to dosing).
•All female subjects, regardless of age, must have negative pregnancy test results at screening and at each baseline.

Exclusion Criteria

•All phases:
•Smokers (use of tobacco products in the previous 3 months). Smokers will be defined who reports tobacco use and/or who has a urine cotinine ≥ 300 ng/ml.
•Open-label safety cohort, Phases A and B:
•Use of prescription and non-prescription medications:
•Open-label safety cohort, Phases A and B: Use of any prescription drugs within 4 weeks prior to study start, and/or over-the-counter (OTC) medication (vitamins, herbal supplements, dietary supplements included) within 2 weeks prior to study start. If needed, acetaminophen is acceptable.
•Phase C: Use of any prescription and/or non-prescription drugs (including vitamins, herbal supplements, and dietary supplements) within 4 weeks prior to study start, unless otherwise specified. If needed, acetaminophen is acceptable.
•Subjects who are using or have used within the last 2 months, any medicine in one or more of the following classes (Phase C only): An HMG coA reductase inhibitor ("statin"), a thiazide-type diuretic, an alpha adrenergic blocker, an anticonvulsant (for example, diphenylhydantoin, phenobarbital or carbamazepine) or a heparin class anticoagulant.
•All Phases (pertaining primarily to post-menopausal females):
•Subjects who are using or have used any medicine in one or more of the following classes:
•Within the last 3 months: Estrogens, Hormone replacement therapy including Selective Estrogens Receptor Modulators (SERMs)

Arms & Interventions

1

ATF936

Intervention: ATF936

2

AXT914

Intervention: AXT914

3

Placebo

Intervention: ATF936

3

Placebo

Intervention: AXT914

Outcomes

Primary Outcomes

Phase B: A head-to-head comparison of ATF936 and AXT914, each given at its pharmacologically effective dose as determined in Phase A.

Phase C: Similarity of PK/PD profile to single-dose profile after limited multiple dosing in healthy post-menopausal females. Early bone biomarker information after multiple dosing for best candidate as selected in Phase A or Phase B

Phase A: Safety and tolerability of single, oral doses of ATF936 and AXT914 under proposed conditions in healthy male and female subjects. Pharmacokinetics (PK) and pharmacodynamics (PD) of ATF936 and AXT914 in healthy male and female subjects.