Pharmacokinetics and Tolerability of Minodronic Acid and Food and Age Effects on the Pharmacokinetics

Pharmacokinetics and Tolerability of Minodronic Acid Tablets in Healthy Chinese Subjects and Food and Age Effects on the Pharmacokinetics

The primary objective of the the study was to evaluate the pharmacokinetic properties of minodronic acid tablets following single and multiple oral administration in healthy Chinese subjects. Additionally, the effects of age and food on minodronic acid pharmacokinetics was also explored.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: minodronic acid

Detailed Description

This was a single-center, phase I study in healthy young (19-30 years) and elderly (60-65 years) volunteers, which was conducted in four parts. In Part 1, minodronic acid tablets were administered to young volunteers at doses of 1, 2, and 4 mg. In Part 2, after a single dose, young volunteers in the 1-mg dose group received repeated oral doses of minodronic acid once daily for 7 days. In Part 3, a single oral dose of minodronic acid 1 mg was administered to elderly volunteers. In part 4, after a washout period of 8 days, volunteers in the 4-mg dose group received a single dose of 4 mg minodronic acid under fed conditions (administrated 30 minutes before high-fat breakfast). Plasma samples were collected and plasma concentrations of minodronic acid were analyzed by LC-MS/MS. Tolerability was assessed throughout the study by physical examinations, vital signs measurement, laboratory analyses, and monitoring of adverse effects.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects were included based on the following criteria:

  • males or females aged 19 to 35 years for young subjects or aged 60 to 65 years for elderly subjects
  • body mass index between 19 and 24 kg/m2
  • thorax radiography and ECG with no abnormalities
  • normal blood pressure values
  • heart rate
  • laboratory test results (hematology, blood biochemistry, hepatic function, and urinalysis)
  • negative test results for HIV and hepatitis B.

Exclusion Criteria:

• Subjects were excluded if they had a heart disease or disorder
• A hepatic, renal, respiratory, immune system, or nervous system disorder

• Any of the following conditions:

  • pregnancy
  • breast-feeding
  • hypocalcemia
  • prescription or over-the-counter medication use (including herbal products) within 2 weeks before the initiation of the study
  • blood donation or participation in other clinical trials within 3 months before enrollment in the study
  • alcohol or drug abuse
  • smoking more than 10 a day
  • clinically significant allergies to drugs or foods
  • sitting blood pressure <80/50 mm Hg or >140/100 mm Hg
  • A ventricular rate <60 beats/min or >100 beats/min at rest.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1-mg group; Twelve healthy young subjects were administered a single oral dose of 1 mg minodronic acid tablets at day 1 and then received repeated oral doses of minodronic acid (1 mg) once daily for 7 days (day 3 to day 9).	Drug: minodronic acid; comparison of different doses, ages and medication conditions; Other Names: YM529/ONO-5920
Experimental: 2-mg group; Twelve healthy young subjects were administered a single oral dose of 2 mg minodronic acid tablets.	Drug: minodronic acid; comparison of different doses, ages and medication conditions; Other Names: YM529/ONO-5920
Experimental: 4-mg group; Twelve healthy young subjects were administered a single oral dose of 4 mg minodronic acid tablets under fasting state at period 1.After a washout period of 8 days, they received the same dosage under fed conditions (administrated 30 minutes before high-fat breakfast).	Drug: minodronic acid; comparison of different doses, ages and medication conditions; Other Names: YM529/ONO-5920
Experimental: 1-mg elderly group; Twelve healthy elderly subjects were administered a single oral dose of 1 mg minodronic acid tablets.	Drug: minodronic acid; comparison of different doses, ages and medication conditions; Other Names: YM529/ONO-5920

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	the maximum observed plasma concentration and	two months
AUC	the area under the concentration-time curve	two months

Secondary Outcome Measures

Outcome Measure	Time Frame
adverse events	two months

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Principal Investigator: Weiyong Li, PhD, Tongji Medical College, Huazhong University of Science and Technology

Publications and helpful links

General Publications

• Zhou Y, He X, Li H, Ni Y, Xu M, Sattar H, Chen H, Li W. Pharmacokinetics and tolerability of minodronic acid tablets in healthy Chinese subjects and food and age effects on the pharmacokinetics. Clin Ther. 2015 Apr 1;37(4):869-76. doi: 10.1016/j.clinthera.2015.01.015. Epub 2015 Mar 5.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: November 12, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (Estimate): November 20, 2014

Study Record Updates

• Last Update Posted (Estimate): November 20, 2014
• Last Update Submitted That Met QC Criteria: November 19, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: age; tolerability; pharmacokinetics; food; Chinese subjects; minodronic acid
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis
• Other Study ID Numbers: WHXH-MINO