Open Label Dose Escalation Phase I Study to Investigate the Safety and Pharmacokinetics of T121E01F and T121E02F in Healthy Postmenopausal Women

NCT01721993 | Completed Phase 1 DMC

• 1 other identifier: THAR2011-1
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

THAR2011-1 is a Phase I, single dose, open-label dose-escalation study to determine the safety, absolute bioavailability, dose proportionality, and pharmacokinetics of T121 in healthy postmenopausal women. The study is expected to identify a safe dose that can be further tested in subsequent multiple dose studies comparing the safety, PK and pharmacodynamics (PD) of T121 with the currently marketed IV zoledronic acid (Zometa).

Conditions

Healthy Postmenopausal Women

Keywords

oral zoledronic acid

Outcome Measures

Primary Outcomes (1)

• PK parameters for a single dose of T121E01F, T121E02F or Zometa and assessment of dose proportionality for T121E01F

  Pharmacokinetic parameters will include maximum serum concentration (Cmax), time corresponding to the occurrence of maximum serum concentration (tmax), area under the serum concentration-time curve from zero to the last observed quantifiable concentration (AUCtlast), area under the serum concentration-time curve from time zero to infinity (AUC), terminal exponential half-life (t1/2,z), absolute bioavailability, cumulative amount recovered in urine (Ae) and renal clearance (CLr).

  48 hours

Secondary Outcomes (1)

• Safety and Tolerability of T121E01F and T121E02F

  7 Days

Study Arms (2)

T121E01F

EXPERIMENTAL

Drug: T121

zoledronic acid IV

ACTIVE COMPARATOR

Drug: Zoledronic acid

Interventions

T121 DRUG

T121E01F

Zoledronic acid DRUG

zoledronic acid IV

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, postmenopausal women between the ages of 35 and 70 years, inclusive. Postmenopausal females (based on medical history) defined as 12 continuous months of spontaneous amenorrhea or bilateral oophorectomy. Women 60 years of age and older will be considered postmenopausal. Women 35-59 must have a serum follicle-stimulating hormone (FSH) result consistent with postmenopausal state.
• Body Mass Index (BMI) of 17.5 to 32 kg/m2; and a total body weight \>50 kg (110 lbs)
• Signed informed consent

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
• History of any severe allergic reaction or known allergy to ZA.
• Evidence or history of any gastrointestinal disease, such as irritable bowel syndrome, Crohn's Disease, chronic gastritis, peptic ulcer disease, H. pylori infection, or other gastrointestinal condition possibly affecting drug absorption.
• History of gastric surgery, including the Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy.
• Evidence or history of any clinically significant cardiovascular (CV) disease or condition, including:
• Any history of a major CV event (myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack);
• Any history of a significant cardiac arrhythmia, implanted artificial pacemaker;
• Blood pressure greater than 150/90 and heart rate greater than 100 at screening;
• Clinically significant abnormalities on 12-lead ECG, including QTc \>450 msec (heart-rate corrected using the Fridericia formula) at Screening.
• History of any autoimmune disease (e.g., systemic lupus erythematosus \[SLE\], scleroderma, psoriasis, vitiligo, primary biliary cirrhosis, etc.).
• Active/ongoing endocrine disorders (e.g., type 1 diabetes, adrenal insufficiency, hypoparathyroidism, etc.) except well controlled thyroid disease and type II diabetes with HgbA1C \<8 are permitted.
• Mucolipidosis type IV.
• Any clinically significant hematological condition (e.g., pernicious anemia).
• Evidence or history of any other severe acute or chronic medical (including renal, pulmonary, hepatic, neurologic, psychiatric, etc.) disease or condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• History or evidence of Paget's disease of bone (osteitis deformans) or related disorder.

Sponsors & Collaborators

• Thar Pharmaceuticals, Inc: lead

Study Sites (1)

Prism Clinical Research

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Interventions

Zoledronic Acid

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mark A Matson, MD

  Prism Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 6, 2012
• Study Start: January 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 26, 2015

Record last verified: 2015-03

Locations

US (1)