Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Effects of Single and Multiple-Doses of ATF936 and AXT914 Administered Orally in Healthy Subjects.

NCT00417261 | Completed Phase 1

• 1 other identifier: CATF936A2201
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

ATF936, AXT914, healthy subjects, pharmacokinetics, parathyroid hormone, osteoporosis; Healthy male and female subjects

Outcome Measures

Primary Outcomes (3)

• 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.

• 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

Study Arms (3)

1

EXPERIMENTAL

ATF936

Drug: ATF936

2

EXPERIMENTAL

AXT914

Drug: AXT914

3

PLACEBO COMPARATOR

Placebo

Drug: ATF936; Drug: AXT914

Interventions

ATF936 DRUG

1; 3

AXT914 DRUG

2; 3

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Study population:
• 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.
• At screening and initial baseline, Vital signs in supine position should be within the following ranges: Oral body temperature: 35.0-37.5 °C (inclusive), Systolic blood pressure: 80 - 150 mm Hg (inclusive), Diastolic blood pressure: 50 - 90 mm Hg (inclusive), Pulse rate: 40 - 90 bpm (inclusive)
• Subjects must weigh at least 60 kg to participate in the study.
• Body Mass Index:
• Open-label safety cohort, Phases A and B: Subjects must have a body mass index (BMI) within the range of 18 to 28 kg/m2, inclusive (a BMI of up to 30 kg/m2 is permissible only if it can be demonstrated that recruitment is being hindered by having an upper limit of 28 kg/m2).
• Phase C: Subjects must have a body mass index (BMI) strictly within the range of 18 to 28 kg/m2 (inclusive).
• Vitamin D 25-(OH) serum level of ≥ 15 ng/ml (for subjects in Phase C at Screening only).

You may not qualify if:

• 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)
• Within the last 12 months: Strontium ranelate, PTH, Calcitonin, Aluminum supplements
• Within the last 24 months: Bisphosphonates (no bisphosphonate use permitted in last 24 months)
• Subjects with cancer or history of malignancy of any organ system, treated or untreated, at any time, whether or not there is evidence of local recurrence or metastases. \[NOTE - the following exceptions will apply: Basal cell or squamous cell carcinoma of the skin or colonic polyps with non-invasive malignancy that have been removed and not recurred, and carcinoma in-situ (CIS) of either the breast, cervix or uterus that has been surgically removed and has not recurred\].
• History or clinical evidence of abnormal thyroid function or thyroid disease (hypo-or-hyperthyroidism, TBG deficiency, etc.) or other endocrine disorders or conditions.
• Subjects with bony deformities and/or neuromuscular irritability indicative of chronic hypocalcaemia.

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Novartis Investigative Site

East Hanover, New Jersey, 07936-1080, United States

Location

MeSH Terms

Conditions

Osteoporosis

Interventions

ATF936; AXT914

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Novartis

  Investigator site

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 28, 2006
• First Posted: December 29, 2006
• Study Start: November 1, 2006
• Study Completion: April 1, 2008
• Last Updated: June 23, 2008

Record last verified: 2008-06

Locations

US (1)