China HVT Safety, PK, PD

NCT02135640 | Completed Phase 1

• 1 other identifier: 114197
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of denosumab administered subcutaneously to healthy adults in China.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (1)

• adverse events

  subjects incidence of treatment adverse events, including clinically-significant changes in physical examinations, laboratory safety tests, ECG and vital signs

  up to 26 weeks

Secondary Outcomes (2)

• PK parameter estimates

  up to 19 weeks

• PD parameter estimateds

  up to 19 weeks

Study Arms (3)

denosumab 60 mg

EXPERIMENTAL

solution

Drug: denosumab 60mg

denosumab 120 mg

EXPERIMENTAL

solution

Drug: denosumab 120 mg

placebo

PLACEBO COMPARATOR

solution

Drug: placebo

Interventions

denosumab 60mg DRUG

solution

denosumab 60 mg

denosumab 120 mg DRUG

solution

denosumab 120 mg

placebo DRUG

solution

placebo

Eligibility Criteria

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

You may qualify if:

• Resident in China and of Chinese ancestry.
• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \> 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 65 years of age, inclusive, from date of birth, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\< 140 pmol/L) is confirmatory.
• OR Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception for the duration of the study and for a minimum of 6 months after the last dose of study medication.
• Body weight of at least 50 kg and body mass index (BMI) from 19 to 24 kg/m2 at time of screening.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Average QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.

You may not qualify if:

• A prior history or current evidence of osteomyelitis or ONJ.
• An active dental or jaw condition that requires oral surgery.
• A planned invasive dental procedure during the course of the study.
• A non-healed dental or oral surgery.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• A positive test for syphilis at Screening.
• Abnormal serum calcium: current hypocalcemia or hypercalcemia. Albumin-adjusted serum calcium levels must be within the normal range of the central laboratory.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \> 14 drinks/week for men or \> 7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 150 ml (5 ounces) of table wine or 360 ml (12 ounces) of beer or 45 ml (1.5 ounces) of 80 proof distilled spirits.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• History of sensitivity to any of the study medications, especially known sensitivity to mammalian-derived drug preparations, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Shanghai, 200030, China

Location

Related Publications (1)

• Chen Q, Hu C, Liu Y, Song R, Zhu W, Zhao H, Nino A, Zhang F, Liu Y. Pharmacokinetics, pharmacodynamics, safety, and tolerability of single-dose denosumab in healthy Chinese volunteers: A randomized, single-blind, placebo-controlled study. PLoS One. 2018 Jun 22;13(6):e0197984. doi: 10.1371/journal.pone.0197984. eCollection 2018.

  PMID: 29933364 DERIVED

Related Links

• Results for study 114197 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Osteoporosis

Interventions

Denosumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2014
• First Posted: May 12, 2014
• Study Start: July 17, 2014
• Primary Completion: February 17, 2015
• Study Completion: February 17, 2015
• Last Updated: May 10, 2017

Record last verified: 2017-05

Locations

CN (1)