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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01590446
• Date of registration: 14/03/2012
• Prospective Registration: No
• Primary sponsor: BioMarin Pharmaceutical
• Public title: A Study to Evaluate Safety and Tolerability of BMN 111 Administered to Healthy Adult Volunteers
• Scientific title: A Phase 1, Two-Part, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of BMN 111 Administered to Healthy Adult Volunteers
• Date of first enrolment: February 2012
• Target sample size: 74
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01590446
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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.

- Has donated > 50 mL of blood or plasma within 60 days prior to study treatment
administration.

- Has a positive urine drug screen or alcohol breath test result during Screening or
upon admission to the research facility.

- Has used nicotine or tobacco-containing products (snuff, chewing tobacco,
cigarettes,cigars, pipes, and nicotine replacements) within 90 days of the first dose
of study treatment as confirmed by urine cotinine screen.

- Has a positive cotinine test result during Screening or upon admission to the
research facility.

- Has a history of any clinically significant neurological, gastrointestinal, renal,
hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine,
hematological, or other major disorders as determined by the Investigator.

- Has had a clinically significant illness within 4 weeks of administration of the
first dose of study treatment as determined by the Investigator.

- Is being treated with a concomitant medication that prolongs the QT/QTc interval
within 7 days or 3 half-lives, whichever is longer, prior to the Screening Visit.

- Has AST or ALT greater than 3xULN or total bilirubin greater than 2xULN.

- Has known hypersensitivity to BMN 111 or its excipients.

- Has partner planning to become pregnant at any time during the study.

- Has any condition that, in the view of the Investigator, places the subject at high
risk of poor treatment compliance or of not completing the study.



Age minimum: 22 Years
Age maximum: 45 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Achondroplasia

Intervention(s)

Drug: BMN 111

Drug: Normal Saline

Primary Outcome(s)

Safety based on vitals signs [Time Frame: 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 [Time Frame: 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 Outcome(s)

Safety based on cardiovascular effects [Time Frame: 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]

Pharmacokinetics [Time Frame: Daily on dosing days Assessed during Part 1 for approximately 10 days and during Part 2 for approximately 24 days]

Secondary ID(s)

111-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors