One Week Comparison Study of PTH and PTHrP Infusions

NCT01333267 | Withdrawn Phase 1 DMC

• 1 other identifier: PRO10060214
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium. These results will be compared to previous studies of Caucasian volunteers.

Conditions

Osteoporosis; Hypercalcemia of Malignancy; Hyperparathyroidism; Bone Diseases, Endocrine

Keywords

Endocrine System Diseases; MusculoSkeletal System Disease; Hormones; Postmenopausal Women; Bone metabolism; Physiologic Properties; African-Americans

Outcome Measures

Primary Outcomes (1)

• Safety: The absence of any dose limiting toxicity (DLT) criteria consisting of one major criteria or two minor criteria.

  one week

Secondary Outcomes (1)

• Blood collections analyzed for measurements of PTH(1-34), PTH(1-84), 25-OH vitamin D, 1,25(OH)2 vitamin D, markers of bone metabolism, and fractional excretion of calcium measurements.

  one week

Study Arms (2)

PTHrP group

EXPERIMENTAL

Subjects receive PTHrP(1-36) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTHrP doses.

Drug: Parathyroid Hormone-related Protein (1-36); Drug: PTH (1-34) and PTHrP (1-36)

PTH dosing group

EXPERIMENTAL

Subjects receive PTH(1-34) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTH doses.

Drug: parathyroid hormone (1-34); Drug: PTH (1-34) and PTHrP (1-36)

Interventions

Parathyroid Hormone-related Protein (1-36) DRUG

PTHrP (1-36) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects.

Also known as: PTHrP(1-36), Bone anabolic agents

PTHrP group

parathyroid hormone (1-34) DRUG

PTH (1-34) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects.

Also known as: PTH(1-34), Bone anabolic agent

PTH dosing group

PTH (1-34) and PTHrP (1-36) DRUG

This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium.

Also known as: Parathyroid Hormone-related Protein (1-36), PTHrP(1-36), IND 49,175, Parathyroid Hormone (1-34), PTH (1-34), IND 60,979

PTH dosing group; PTHrP group

Eligibility Criteria

• Age: 24 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy African-American subjects of both sexes between the ages of 24-35 years, who are able to spend one week on the Clinical \& Translational Research Center (CTRC) at the University of Pittsburgh Medical Center (UPMC) Montefiore.

You may not qualify if:

• Subjects with cardiac, vascular, renal (serum creatinine \> 1.5), pulmonary, endocrine, musculoskeletal, hepatic, hematologic, malignant, or rheumatologic disease will be excluded.
• Those found to have vitamin D deficiency, defined as a 25-OH vitamin D level \< 10 ng/mL will also be excluded.
• Additionally, those with BMI \> 30, anemia (hematocrit \< 36% in women, \<40% in men), significant alcohol use, illicit drug use, hypertension (BP\>160/90), or baseline hypotension (systolic blood pressure \< 90mmHg) will be excluded.
• Those taking chronic medications (except oral contraceptive pills (OCP's) or stable doses of thyroid replacement) or those who have received an investigational drug in the past 90 days will also be excluded.
• Prior participants in PTH or PTHrP studies will not be eligible to participate.
• Additionally pregnant women and lactating women will be excluded; all women will have a urine pregnancy test performed immediately before starting the study.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (52)

• Dean T, Vilardaga JP, Potts JT Jr, Gardella TJ. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol Endocrinol. 2008 Jan;22(1):156-66. doi: 10.1210/me.2007-0274. Epub 2007 Sep 13.

  PMID: 17872377 BACKGROUND

• Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia-Ocana A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D. J Bone Miner Res. 2005 Oct;20(10):1792-803. doi: 10.1359/JBMR.050602. Epub 2005 Jun 6.

  PMID: 16160737 BACKGROUND

• Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocana A, Stewart AF. Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. J Clin Endocrinol Metab. 2003 Apr;88(4):1603-9. doi: 10.1210/jc.2002-020773.

  PMID: 12679445 BACKGROUND

• Nelson DA, Jacobsen G, Barondess DA, Parfitt AM. Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men. J Bone Miner Res. 1995 May;10(5):782-7. doi: 10.1002/jbmr.5650100515.

  PMID: 7639113 BACKGROUND

• George A, Tracy JK, Meyer WA, Flores RH, Wilson PD, Hochberg MC. Racial differences in bone mineral density in older men. J Bone Miner Res. 2003 Dec;18(12):2238-44. doi: 10.1359/jbmr.2003.18.12.2238.

  PMID: 14672360 BACKGROUND

• Kalkwarf HJ, Zemel BS, Gilsanz V, Lappe JM, Horlick M, Oberfield S, Mahboubi S, Fan B, Frederick MM, Winer K, Shepherd JA. The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab. 2007 Jun;92(6):2087-99. doi: 10.1210/jc.2006-2553. Epub 2007 Feb 20.

  PMID: 17311856 BACKGROUND

• Hui SL, Dimeglio LA, Longcope C, Peacock M, McClintock R, Perkins AJ, Johnston CC Jr. Difference in bone mass between black and white American children: attributable to body build, sex hormone levels, or bone turnover? J Clin Endocrinol Metab. 2003 Feb;88(2):642-9. doi: 10.1210/jc.2002-020653.

  PMID: 12574194 BACKGROUND

• Bachrach LK, Hastie T, Wang MC, Narasimhan B, Marcus R. Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab. 1999 Dec;84(12):4702-12. doi: 10.1210/jcem.84.12.6182.

  PMID: 10599739 BACKGROUND

• Gilsanz V, Skaggs DL, Kovanlikaya A, Sayre J, Loro ML, Kaufman F, Korenman SG. Differential effect of race on the axial and appendicular skeletons of children. J Clin Endocrinol Metab. 1998 May;83(5):1420-7. doi: 10.1210/jcem.83.5.4765.

  PMID: 9589632 BACKGROUND

• Abrams SA, O'brien KO, Liang LK, Stuff JE. Differences in calcium absorption and kinetics between black and white girls aged 5-16 years. J Bone Miner Res. 1995 May;10(5):829-33. doi: 10.1002/jbmr.5650100521.

  PMID: 7639119 BACKGROUND

• Gilsanz V, Roe TF, Mora S, Costin G, Goodman WG. Changes in vertebral bone density in black girls and white girls during childhood and puberty. N Engl J Med. 1991 Dec 5;325(23):1597-600. doi: 10.1056/NEJM199112053252302.

  PMID: 1944449 BACKGROUND

• Luckey MM, Wallenstein S, Lapinski R, Meier DE. A prospective study of bone loss in African-American and white women--a clinical research center study. J Clin Endocrinol Metab. 1996 Aug;81(8):2948-56. doi: 10.1210/jcem.81.8.8768857.

  PMID: 8768857 BACKGROUND

• Thomas PA. Racial and ethnic differences in osteoporosis. J Am Acad Orthop Surg. 2007;15 Suppl 1:S26-30. doi: 10.5435/00124635-200700001-00008.

  PMID: 17766786 BACKGROUND

• Han ZH, Palnitkar S, Rao DS, Nelson D, Parfitt AM. Effects of ethnicity and age or menopause on the remodeling and turnover of iliac bone: implications for mechanisms of bone loss. J Bone Miner Res. 1997 Apr;12(4):498-508. doi: 10.1359/jbmr.1997.12.4.498.

  PMID: 9101361 BACKGROUND

• Cauley JA, Wampler NS, Barnhart JM, Wu L, Allison M, Chen Z, Hendrix S, Robbins J, Jackson RD; Women's Health Initiative Observational Study. Incidence of fractures compared to cardiovascular disease and breast cancer: the Women's Health Initiative Observational Study. Osteoporos Int. 2008 Dec;19(12):1717-23. doi: 10.1007/s00198-008-0634-y. Epub 2008 Jul 16.

  PMID: 18629572 BACKGROUND

• Cauley JA, Palermo L, Vogt M, Ensrud KE, Ewing S, Hochberg M, Nevitt MC, Black DM. Prevalent vertebral fractures in black women and white women. J Bone Miner Res. 2008 Sep;23(9):1458-67. doi: 10.1359/jbmr.080411.

  PMID: 18442309 BACKGROUND

• Cauley JA, Lui LY, Ensrud KE, Zmuda JM, Stone KL, Hochberg MC, Cummings SR. Bone mineral density and the risk of incident nonspinal fractures in black and white women. JAMA. 2005 May 4;293(17):2102-8. doi: 10.1001/jama.293.17.2102.

  PMID: 15870413 BACKGROUND

• Opotowsky AR, Bilezikian JP. Racial differences in the effect of early milk consumption on peak and postmenopausal bone mineral density. J Bone Miner Res. 2003 Nov;18(11):1978-88. doi: 10.1359/jbmr.2003.18.11.1978.

  PMID: 14606510 BACKGROUND

• Cosman F, Nieves J, Dempster D, Lindsay R. Vitamin D economy in blacks. J Bone Miner Res. 2007 Dec;22 Suppl 2:V34-8. doi: 10.1359/jbmr.07s220.

  PMID: 18290719 BACKGROUND

• Harris SS, Soteriades E, Dawson-Hughes B; Framingham Heart Study; Boston Low-Income Elderly Osteoporosis Study. Secondary hyperparathyroidism and bone turnover in elderly blacks and whites. J Clin Endocrinol Metab. 2001 Aug;86(8):3801-4. doi: 10.1210/jcem.86.8.7783.

  PMID: 11502814 BACKGROUND

• Cosman F, Morgan DC, Nieves JW, Shen V, Luckey MM, Dempster DW, Lindsay R, Parisien M. Resistance to bone resorbing effects of PTH in black women. J Bone Miner Res. 1997 Jun;12(6):958-66. doi: 10.1359/jbmr.1997.12.6.958.

  PMID: 9169356 BACKGROUND

• Fuleihan GE, Gundberg CM, Gleason R, Brown EM, Stromski ME, Grant FD, Conlin PR. Racial differences in parathyroid hormone dynamics. J Clin Endocrinol Metab. 1994 Dec;79(6):1642-7. doi: 10.1210/jcem.79.6.7989469.

  PMID: 7989469 BACKGROUND

• Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr. 2008 Jun;87(6):1952-8. doi: 10.1093/ajcn/87.6.1952.

  PMID: 18541590 BACKGROUND

• Aloia JF. African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. Am J Clin Nutr. 2008 Aug;88(2):545S-550S. doi: 10.1093/ajcn/88.2.545S.

  PMID: 18689399 BACKGROUND

• Aloia JF, Talwar SA, Pollack S, Feuerman M, Yeh JK. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women. Am J Clin Nutr. 2006 Sep;84(3):602-9. doi: 10.1093/ajcn/84.3.602.

  PMID: 16960175 BACKGROUND

• Aloia JF, Talwar SA, Pollack S, Yeh J. A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med. 2005 Jul 25;165(14):1618-23. doi: 10.1001/archinte.165.14.1618.

  PMID: 16043680 BACKGROUND

• Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, Santora AC, Sherwood LM. Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res. 2005 Feb;20(2):185-94. doi: 10.1359/JBMR.041007. Epub 2004 Oct 18.

  PMID: 15647811 BACKGROUND

• Cauley JA, Wu L, Wampler NS, Barnhart JM, Allison M, Chen Z, Jackson R, Robbins J. Clinical risk factors for fractures in multi-ethnic women: the Women's Health Initiative. J Bone Miner Res. 2007 Nov;22(11):1816-26. doi: 10.1359/jbmr.070713.

  PMID: 17638574 BACKGROUND

• Faulkner KA, Cauley JA, Zmuda JM, Landsittel DP, Nevitt MC, Newman AB, Studenski SA, Redfern MS. Ethnic differences in the frequency and circumstances of falling in older community-dwelling women. J Am Geriatr Soc. 2005 Oct;53(10):1774-9. doi: 10.1111/j.1532-5415.2005.53514.x.

  PMID: 16181179 BACKGROUND

• Finkelstein JS, Lee ML, Sowers M, Ettinger B, Neer RM, Kelsey JL, Cauley JA, Huang MH, Greendale GA. Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors. J Clin Endocrinol Metab. 2002 Jul;87(7):3057-67. doi: 10.1210/jcem.87.7.8654.

  PMID: 12107201 BACKGROUND

• Schnitzler CM, Mesquita JM. Cortical bone histomorphometry of the iliac crest in normal black and white South African adults. Calcif Tissue Int. 2006 Dec;79(6):373-82. doi: 10.1007/s00223-006-0053-z. Epub 2006 Dec 8.

  PMID: 17160576 BACKGROUND

• Cummings SR, Cauley JA, Palermo L, Ross PD, Wasnich RD, Black D, Faulkner KG. Racial differences in hip axis lengths might explain racial differences in rates of hip fracture. Study of Osteoporotic Fractures Research Group. Osteoporos Int. 1994 Jul;4(4):226-9. doi: 10.1007/BF01623243.

  PMID: 7949753 BACKGROUND

• Perry HM 3rd, Horowitz M, Morley JE, Fleming S, Jensen J, Caccione P, Miller DK, Kaiser FE, Sundarum M. Aging and bone metabolism in African American and Caucasian women. J Clin Endocrinol Metab. 1996 Mar;81(3):1108-17. doi: 10.1210/jcem.81.3.8772584.

  PMID: 8772584 BACKGROUND

• Jacobsen SJ, Goldberg J, Miles TP, Brody JA, Stiers W, Rimm AA. Race and sex differences in mortality following fracture of the hip. Am J Public Health. 1992 Aug;82(8):1147-50. doi: 10.2105/ajph.82.8.1147.

  PMID: 1636840 BACKGROUND

• Mikuls TR, Saag KG, George V, Mudano AS, Banerjee S. Racial disparities in the receipt of osteoporosis related healthcare among community-dwelling older women with arthritis and previous fracture. J Rheumatol. 2005 May;32(5):870-5.

  PMID: 15868624 BACKGROUND

• Alam NM, Archer JA, Lee E. Osteoporotic fragility fractures in African Americans: under-recognized and undertreated. J Natl Med Assoc. 2004 Dec;96(12):1640-5.

  PMID: 15624249 BACKGROUND

• Looker AC. The skeleton, race, and ethnicity. J Clin Endocrinol Metab. 2002 Jul;87(7):3047-50. doi: 10.1210/jcem.87.7.8779. No abstract available.

  PMID: 12107199 BACKGROUND

• Bell NH, Bilezikian JP, Bone HG 3rd, Kaur A, Maragoto A, Santora AC; MK-063 Study Group. Alendronate increases bone mass and reduces bone markers in postmenopausal African-American women. J Clin Endocrinol Metab. 2002 Jun;87(6):2792-7. doi: 10.1210/jcem.87.6.8575.

  PMID: 12050252 BACKGROUND

• Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10;344(19):1434-41. doi: 10.1056/NEJM200105103441904.

  PMID: 11346808 BACKGROUND

• Lau EM, Suriwongpaisal P, Lee JK, Das De S, Festin MR, Saw SM, Khir A, Torralba T, Sham A, Sambrook P. Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study. J Bone Miner Res. 2001 Mar;16(3):572-80. doi: 10.1359/jbmr.2001.16.3.572.

  PMID: 11277276 BACKGROUND

• Awumey EM, Mitra DA, Hollis BW, Kumar R, Bell NH. Vitamin D metabolism is altered in Asian Indians in the southern United States: a clinical research center study. J Clin Endocrinol Metab. 1998 Jan;83(1):169-73. doi: 10.1210/jcem.83.1.4514.

  PMID: 9435436 BACKGROUND

• Looker AC, Orwoll ES, Johnston CC Jr, Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res. 1997 Nov;12(11):1761-8. doi: 10.1359/jbmr.1997.12.11.1761.

  PMID: 9383679 BACKGROUND

• Wright NM, Papadea N, Willi S, Veldhuis JD, Pandey JP, Key LL, Bell NH. Demonstration of a lack of racial difference in secretion of growth hormone despite a racial difference in bone mineral density in premenopausal women--a Clinical Research Center study. J Clin Endocrinol Metab. 1996 Mar;81(3):1023-6. doi: 10.1210/jcem.81.3.8772569.

  PMID: 8772569 BACKGROUND

• Heaney RP. Bone mass, the mechanostat, and ethnic differences. J Clin Endocrinol Metab. 1995 Aug;80(8):2289-90. doi: 10.1210/jcem.80.8.7629221. No abstract available.

  PMID: 7629221 BACKGROUND

• Cundy T, Cornish J, Evans MC, Gamble G, Stapleton J, Reid IR. Sources of interracial variation in bone mineral density. J Bone Miner Res. 1995 Mar;10(3):368-73. doi: 10.1002/jbmr.5650100306.

  PMID: 7785457 BACKGROUND

• Wright NM, Renault J, Willi S, Veldhuis JD, Pandey JP, Gordon L, Key LL, Bell NH. Greater secretion of growth hormone in black than in white men: possible factor in greater bone mineral density--a clinical research center study. J Clin Endocrinol Metab. 1995 Aug;80(8):2291-7. doi: 10.1210/jcem.80.8.7543111.

  PMID: 7543111 BACKGROUND

• Looker AC, Johnston CC Jr, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Lindsay RL. Prevalence of low femoral bone density in older U.S. women from NHANES III. J Bone Miner Res. 1995 May;10(5):796-802. doi: 10.1002/jbmr.5650100517.

  PMID: 7639115 BACKGROUND

• Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay RL. Proximal femur bone mineral levels of US adults. Osteoporos Int. 1995;5(5):389-409. doi: 10.1007/BF01622262.

  PMID: 8800790 BACKGROUND

• Villa ML. Cultural determinants of skeletal health: the need to consider both race and ethnicity in bone research. J Bone Miner Res. 1994 Sep;9(9):1329-32. doi: 10.1002/jbmr.5650090902. No abstract available.

  PMID: 7817815 BACKGROUND

• Baron JA, Barrett J, Malenka D, Fisher E, Kniffin W, Bubolz T, Tosteson T. Racial differences in fracture risk. Epidemiology. 1994 Jan;5(1):42-7. doi: 10.1097/00001648-199401000-00008.

  PMID: 8117781 BACKGROUND

• Silverman SL, Madison RE. Decreased incidence of hip fracture in Hispanics, Asians, and blacks: California Hospital Discharge Data. Am J Public Health. 1988 Nov;78(11):1482-3. doi: 10.2105/ajph.78.11.1482.

  PMID: 3177728 BACKGROUND

• Looker AC, Flegal KM, Melton LJ 3rd. Impact of increased overweight on the projected prevalence of osteoporosis in older women. Osteoporos Int. 2007 Mar;18(3):307-13. doi: 10.1007/s00198-006-0241-8. Epub 2006 Oct 20.

  PMID: 17053871 BACKGROUND

MeSH Terms

Conditions

Osteoporosis; Humoral Hypercalcemia Of Malignancy; Hyperparathyroidism; Bone Diseases, Endocrine; Endocrine System Diseases; Musculoskeletal Diseases

Interventions

parathyroid hormone-related peptide (1-36); Parathyroid Hormone; Parathyroid Hormone-Related Protein

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Parathyroid Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors

Study Officials

• Mara J. Horwitz, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, University of Pittsburgh School of Medicine

Study Record Dates

• First Submitted: April 8, 2011
• First Posted: April 11, 2011
• Study Start: January 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: December 5, 2014

Record last verified: 2014-12

Locations

US (1)