A Trial Evaluating Safety, Tolerability and Pharmacokinetics of Subcutaneous Single Doses of ACP-015 in Healthy Adult Male Subjects.

Exclusion Criteria32

• Participation in any investigational medication or device trials within 90 days or 5 half-lives (whichever is longer) prior to screening (and during enrollment in current trial)
• Prior participation in investigation trial (at any time) involving use of vosoritide
• History or presence of malignant disease, other than basal cell epithelioma/carcinoma or completely resected squamous skin cancer with no recurrence for 12 months
• Any history of significant bone disorders including (but not limited to) osteoporosis, hypo- or hyperparathyroidism, or inherited skeletal dysplasias
• Baseline systolic blood pressure less than 90 mm Hg
• Past history of, or presence of orthostatic hypotension defined as a decrease of more than or equal to 20 mm Hg systolic blood pressure or more than 20 bpm increase in heart rate at 3 minutes of standing), or with symptoms of lightheadedness, dizziness, or fainting upon standing at screening. the more than 20bpm increase in heart rate upon standing must result in a heart rate of more than 120 bpm or be considered clinically significant by the investigator.
• Subject has electrographically significant abnormalities that might interfere with ECG analysis including evidence of a previous MI, LVH, flat T waves (particularly in the inferior leads) or more than minor non- specific ST-T wave changes or:
• QRS more than 110 msec
• QT interval corrected using Fridericia’s formula (QTcF) more than 440 msec (men and women)
• PR interval more than 220 msec
• Heart rate less than 50 BPM or more than 90 BPM
• Complete right bundle branch block or left bundle branch block.
• Subject has a history of, disease or dysfunction of the pulmonary, cardiovascular, endocrine, hematologic, neurological, immune, gastrointestinal, genitourinary, or other body system, that is clinically significant in the opinion of the Investigator, including
• Anemia
• Pathologic factures
• Diabetes mellitus, Type I or II
• History of drug abuse (including alcoholism) or positive drug screen during screening
• History of cardiac or valvular disease (including hypertension or hypotension)
• Acute illness that can affect hydration or volume status [such as that associated with decreased nutritional intake or increased volume loss (such as diarrhea)]
• Known hypersensitivity to the components of the trial medication (trehalose, tris(hydroxymethyl)aminomethane, succinate and PEG)
• Poor peripheral venous access
• Planned procedure or surgery during the course of the study
• Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule (including non-compliance)
• Subject uses any prescription drug or over-the-counter medication, including herbals or routine vitamins or minerals, within 7 days prior to check-in (or 14 days if the drug is a potential inducer or inhibitor of cytochrome P450 [CYP] 3A4 or P-glycoprotein [P gp] [eg, St. John’s Wort, rifampin, cyclosporine, or ritonavir]) or 5 half-lives (whichever is longer) or subject requires continued use of a prescription drug or over-the-counter medication during study participation, with the exception of over-the-counter analgesics (eg, occasional [less than 2 times/week] acetaminophen, ibuprofen, naproxen]
• Subject is unwilling to refrain from strenuous exercise from 7 days prior to check-in through completion of the study
• Subject is unwilling to abstain from ingestion of caffeine or xanthine-containing products (eg, tea, coffee, chocolate, cola, etc.) beginning 96 hours prior to check-in until discharge and within 96 hours prior to each visit
• Subject is unwilling to abstain from alcohol beginning 48 hours prior to check-in through completion of the study
• Subject has a history of high alcohol consumption within 6 months prior to Screening, defined as an average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine, or 1 measure (25 mL) of spirits
• Subject uses or has used nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff, etc.) within 6 months prior to Screening and/or is unwilling to abstain from using nicotine-containing products until the end of the study
• Subject is unwilling to abstain from consuming grapefruit and/or grapefruit juice within 14 days prior to check-in and is unwilling to abstain from consuming grapefruit and/or grapefruit juice until the end of the study.
• Subject is unwilling to abstain from consuming other fruit juices within 48 hours prior to check-in and is unwilling to abstain from these items within 48 hours prior to each study visit
• Subject is unwilling to abstain from consuming cruciferous vegetables (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussel sprouts, or mustard greens) or charbroiled meats within 7 days prior to check-in and is unwilling to abstain from these items until the end of the study