A Study to Evaluate Safety and Tolerability of BMN 111 Administered to Healthy Adult Volunteers

NCT01590446 | Completed Phase 1

• 1 other identifier: 111-101
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure how much of the study drug gets into the blood- stream and how long it takes the body to get rid of it when given as a single dose. Information about any side effects that may occur will also be collected.

Conditions

Achondroplasia

Keywords

Achondroplasia

Outcome Measures

Primary Outcomes (2)

• Safety based on vitals signs

  Daily throughout the study Assessed for approximately 8 days following each single dose in Part 1, and for approximately 24 days following each daily dose in Part 2

• Safety based on adverse events

  Daily throughout the study Assessed for approximately 8 days following each single dose in Part 1, and for approximately 24 days following each daily dose in Part 2

Secondary Outcomes (2)

• Pharmacokinetics

  Daily on dosing days Assessed during Part 1 for approximately 10 days and during Part 2 for approximately 24 days

• Safety based on cardiovascular effects

  Daily throughout the study Assessed for approximately 8 days following each single dose in Part 1, and for approximately 24 days following each daily dose in Part 2

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Normal Saline

BMN 111

ACTIVE COMPARATOR

Drug: BMN 111

Interventions

BMN 111 DRUG

SC injection, Part 1 single dose and Part 2 multiple dose.

Also known as: Modified C-Natriuretic Peptide, ProCNP38

BMN 111

Normal Saline DRUG

SC injection, Part 1 single dose and Part 2 multiple dose

Placebo

Eligibility Criteria

• Age: 22 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is willing and able to provide written, signed informed consent (legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure.
• Is a male 22 to 45 years of age, inclusive
• Has a body weight between 63 and 100 kg, inclusive
• Has a body mass index (BMI) between 18 and 32 kg/m2, inclusive
• Is able and willing to abstain from nicotine, alcohol, methylxanthine-containing beverages or food (e.g., coffee, tea, colas, chocolate, energy drinks), poppy seeds, and grapefruit juice for 48 hours prior to admission and for the duration of the study
• Is in good health generally, as determined by medical history, physical examination, clinical laboratory evaluations, and 12-lead electrocardiogram (ECG) at Screening
• Is willing and able to perform all study procedures as physically possible
• If sexually active, is willing to use a condom during sexual intercourse with female partners and to have their female partners use an additional effective means of contraception (e.g., intrauterine device, coil, diaphragm plus spermicide, oral contraceptive) or to abstain from sexual intercourse if female partner is not surgically sterile by tubal occlusion (ligation or occluding device) or postmenopausal from time of initial admission to the research facility until their last study visit

You may not qualify if:

• Baseline systolic blood pressure \< 100 mmHg
• Subjects with spontaneous orthostatic hypotension, including a systolic decline of \> 20 or diastolic change of \> 10 mmHg or heart rate increase of \> 30 bpm
• Has renal insufficiency as determined by eGFR \< 65 mL/min/1.73m2 using the revised Cockcroft-Gault calculation: (140 - age \[y\])
• body weight \[kg\] / 72 serum creatinine \[mg/dL\]
• Has anemia (Hb \< 12.5 gm/dL)
• Has history of cardiac or vascular disease, including the following: Congenital heart disease; Hypertension or hypotension; Cerebrovascular disease; aortic insufficiency; Clinically significant atrial or ventricular arrhythmias; Cardiac valvular heart disease; Hypertrophic cardiomyopathy or other cardiomyopathy
• Has a Screening ECG showing any of the following: Resting heart rate \< 45 or \> 100 bpm; PR interval \> 210 msec; P wave duration \> 120 msec; QRS interval \< 70 or \> 120 msec; Corrected QTc \> 440 msec; QRS axis outside the range of -30 + 100 degrees; Right or left atrial enlargement or ventricular hypertrophy; Second- or third-degree atrioventricular block
• Heart block or intraventricular conduction defect
• Has diabetes mellitus Type I or Type II
• Is being treated with angiotensin-converting enzyme inhibitors, antihypertensive medications, diuretics, calcium-channel blockers, beta-blockers, cardiac glycosides, systemic anticholinergic agents, or drugs that may impair or enhance compensatory tachycardia
• Is being treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids.
• Has any acute illness associated with volume dehydration (e.g., nausea/vomiting/diarrhea).
• Uses of any prescription medications, over-the-counter medications, or nutritional supplements within 10 days prior to dosing.
• Uses any other investigational product or investigational medical device within 90 days prior to screening or requires any investigational agent prior to completion of all scheduled study assessments.
• Consumes at least 14 units/week of alcohol (1 unit approximates 360 mL beer, 100 mL wine, or 35 mL spirits) or has significant history of alcoholism or drug/chemical abuse as determined by the Investigator.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (1)

Covance CRU Inc.

Evansville, Indiana, 47710, United States

Location

MeSH Terms

Conditions

Achondroplasia

Interventions

vosoritide; Saline Solution

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2012
• First Posted: May 3, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: June 11, 2012

Record last verified: 2012-06

Locations

US (1)