Safety and tolerability of single and multiple-ascending doses of the study drug ACP-014 in Healthy volunteers.

INTERVENTION: Participants will be enrolled to 1 of the following 3 interventions: In Part 1 of the trial, comprising up to 8 single ascending dose (SAD) cohorts of 10 subjects each, study drug is administered SC in the abdomen in single doses to ascending dose cohorts [3.5µg, 12 µg, 32 µg, 48 µg, 72 µg, 100 µg, 124 µg, and 152 µg ACP‐014 (N=8) or placebo (N=2)] until dose limiting toxicity (DLT) is observed. Cohort X‐ After completion of the SAD cohorts, up to 16 subjects will be enrolled in the subsequent 2 by 2 randomized crossover cohort. 8 subjects (optimally 4 males and 4 females) will receive single SC doses of 12 µgACP‐014 in either the abdomen/thigh (A/T) or the thigh/abdomen (T/A) in a crossover fashion. The other 8 subjects (optimally 4 males and 4 females) will receive the highest tolerated single dose of ACP‐014 in either A/T or T/A in a crossover fashion to obtain initial information on potential PK differences between SC dosing in the abdomen vs. the thigh. All subjects will receive two single doses of ACP‐014 at least 7 days apart. In Part 2, study drug is administered SC in the abdomen daily for 10 days to approximate steady‐state to up to 9 multiple ascending dose (MAD) cohorts of 10 subjects each (8 subjects receiving ACP‐014 , and 2 subjects receiving placebo). The initial dose cohort of 3.5 µg ACP‐014 daily may begin after completion of the 32 µg SAD cohort, based on an expected accumulation ratio of 3 plus an additional 10‐fold safety margin. The 2nd MAD dose will be 7.0 µg/day, followed by 12 µg/day, 16 µg/day, 20 µg/day, 24 µg/day, 32 µg/day, 40µg/day and potentially 48 µg/day. CONDITION: Hypoparathyroidism PRIMARY OUTCOME: To assess the safety and tolerability of single and multiple daily doses of ACP‐014 in healthy adult subjects. SECONDARY OUTCOME: Cohort X only: To compare PK between subcutaneous (SC) injection of ACP‐014 in the abdomen vs. the thigh To assess whether ACP‐014 treatment reduces urine calcium excretion in healthy adult subjects To determine the incidence of antiPTH and antiPEG antibodies To evaluate the pharmacodynamics (PD) and pharmacokinetics (PK) following single and multiple daily doses of ACP‐014 INCLUSION CRITERIA: 1) Healthy adult males and females aged 18‐60 years 2) Body mass index (BMI) 18.5 – 27 kg/m2 3) Able to provide informed consent 4) All male and females of childbearing potential must agree to use a barrier method of contraception from the time of signing informed consent until 30 days after study completion if engaging in sexual activity, unless a female of childbearing potential has been using a non‐barrier highly effective forms of contraception including oral contraceptive pills, long‐acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device and agrees to continue this form of contraception until 30 days after study completion, or has had a tubal ligation, or their male partner has had a vasectomy. Subjects with same sex partners (abstinence from penile‐vaginal intercourse) are eligible when this is their preferred and usual lifestyle. Male subjects must use contrace