Investigating a New Way of Giving Medicine to Newborn and Preterm Babies

NCT01676844 | Unknown Phase 2

• 2 other identifiers: UEC1112/652012-003625-19
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

There is a deficit in the number of 'age-appropriate' formulations available for the delivery of medicines to children. Liquid preparations are considered the 'gold standard' for delivering medicines to children however many of these are formulated using ingredients which can be toxic to children (e.g. preservatives, alcohols), particularly to neonatal babies (\< 4 weeks old) who do not possess the metabolic processes and mature organ function of older children or adults. Rapidly dissolving oral thin films (OTFs) dissolve quickly in the saliva, releasing the active ingredient(s) without the need for chewing or water, making them ideally suited to patients who find it difficult to swallow other oral dosage forms such as tablets or capsules. The aim of this study is to demonstrate that OTFs can offer a safe and effective alternative for oral administration of phosphate supplements to neonatal infants for the treatment of hypophosphataemia and osteopenia of prematurity. It is hypothesised that this treatment will be equal to standard therapy using an oral solution. Babies born before 32 weeks gestational age are routinely supplemented with oral phosphate as soon as they have been established on oral feeds in order to prevent bone disorders such as osteopenia. Babies recruited to this study will be given phosphate supplementation as per NHS Greater Glasgow and Clyde guidelines. This single-centre cross-over study will take place in the intensive care and special care baby units at the Princess Royal Maternity in Glasgow. The investigators aim to recruit 20-30 babies and will use blood phosphate levels (obtained from routine sampling only) to evaluate treatment effect. Babies will be randomised to receive either OTFs or oral solution of potassium acid phosphate for 2 weeks followed by 2 weeks of the other therapy. The investigators hypothesise that OTF treatment will be equivalent to standard oral solution.

Conditions

Hypophosphataemia; Osteopenia of Prematurity

Keywords

Phosphorus; Phosphate; Hypophosphataemia; Osteopenia; Prematurity

Outcome Measures

Primary Outcomes (1)

• Serum phosphate

  The aim of this research is to demonstrate that oral thin films (OTFs) containing potassium acid phosphate are equivalent to standard oral phosphate supplementation using an oral solution in the prevention of hypophosphataemia (low blood phosphorus). The primary outcome measure will be plasma phosphate. We will assume an equivalent therapeutic effect using OTFs if individual plasma levels for these babies are found to lie within an acceptable physiological range, and the difference between the means of the two groups (as determined by a statistical t-test) lies within 20% of the mean plasma level for the control group.

  Participants will be followed from birth until the end of the study period, approximately 6 weeks on average

Secondary Outcomes (1)

• Age-appropriateness

  Participants will be followed from birth until the end of the study period, approximately 6 weeks on average

Study Arms (2)

Oral thin film therapy

EXPERIMENTAL

One or more oral thin films (OTFs) containing potassium acid phosphate administered to the inside cheek, tongue or palate at a dose of 0.5 mmol/kg body weight twice daily. Dosages will be rounded to the nearest 0.1 mM/kg. Where more than one OTF is required to achieve a dosage of 0.5mmol/kg, strips will be administered consecutively with time allowed between doses to allow for complete dissolving of the previous strip. Treatment will continue until the participant has received OTF therapy for 14 consecutive days.

Drug: Oral thin film therapy (Potassium acid phosphate oral thin films)

Standard therapy

ACTIVE COMPARATOR

Standard oral phosphate supplementation as per NHS Greater Glasgow and Clyde Guidelines. An oral solution containing potassium acid phosphate (1 mmol/mL) will be administered at a dosage of 0.5 mM/kg body weight twice daily. Dosages will be rounded to the nearest 0.1 mM/kg. Standard therapy will continue until the participant has received treatment for 14 consecutive days.

Drug: Standard therapy (Potassium acid phosphate oral solution)

Interventions

Oral thin film therapy (Potassium acid phosphate oral thin films) DRUG

Orally dissolving thin film. White, square oral thin film. 15 mm x 15 mm surface area. 1-2 mm film thickness. No markings. Place a single OTF on the tongue, inside cheek or palate and allow to dissolve.

Also known as: Potassium acid phosphate oral thin films 0.2, 0.3 and 0.4 mM

Oral thin film therapy

Standard therapy (Potassium acid phosphate oral solution) DRUG

Each millilitre contains approximately 136mg Monobasic Potassium Phosphate Ph.Eur. (KH2PO4) equivalent to 1mmol Potassium (39mg) and 1mmol Phosphate (31mg Phosphorus). Manufacturer: Specials Products Ltd., Surrey, UK.

Also known as: Potassium acid phosphate 1mmol in 1ml oral solution

Standard therapy

Eligibility Criteria

• Age: 26 Weeks - 40 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• GENDER Male or female
• AGE Born \< 32 completed weeks' gestational age
• CONSENT Parents/other caregivers demonstrate understanding of the study and willingness to consent to their child's participation as evidenced by voluntary written informed consent (signed and dated) obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
• MEDICATIONS AND TREATMENTS Participants must have been established on oral feeds (as defined by as \> 75% of predicted volume enterally for three consecutive days).

You may not qualify if:

• MEDICATIONS Patients prescribed concomitant medication known to interact with potassium phosphate or any of the other ingredients in the oral thin film.
• CLINICAL STUDIES
• Previous participation in this study.
• Subject whose participation in this study will result in a participation in more than four studies over a twelve month period.

Sponsors & Collaborators

• University of Strathclyde: lead

Study Sites (1)

Princess Royal Maternity

Glasgow, Strathclyde, G31 2ER, United Kingdom

Location

Related Publications (9)

• Conroy S, McIntyre J. The use of unlicensed and off-label medicines in the neonate. Semin Fetal Neonatal Med. 2005 Apr;10(2):115-22. doi: 10.1016/j.siny.2004.11.003. Epub 2005 Jan 25.

  PMID: 15701577 BACKGROUND

• Lyon AJ, McIntosh N, Wheeler K, Brooke OG. Hypercalcaemia in extremely low birthweight infants. Arch Dis Child. 1984 Dec;59(12):1141-4. doi: 10.1136/adc.59.12.1141.

  PMID: 6441525 BACKGROUND

• Mitchell SM, Rogers SP, Hicks PD, Hawthorne KM, Parker BR, Abrams SA. High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support. BMC Pediatr. 2009 Jul 29;9:47. doi: 10.1186/1471-2431-9-47.

  PMID: 19640269 BACKGROUND

• Zhong B. How to calculate sample size in randomized controlled trial? J Thorac Dis. 2009 Dec;1(1):51-4.

  PMID: 22263004 BACKGROUND

• Marks J, Srai SK, Biber J, Murer H, Unwin RJ, Debnam ES. Intestinal phosphate absorption and the effect of vitamin D: a comparison of rats with mice. Exp Physiol. 2006 May;91(3):531-7. doi: 10.1113/expphysiol.2005.032516. Epub 2006 Jan 23.

  PMID: 16431934 BACKGROUND

• Walton J, Gray TK. Absorption of inorganic phosphate in the human small intestine. Clin Sci (Lond). 1979 May;56(5):407-12. doi: 10.1042/cs0560407.

  PMID: 477225 BACKGROUND

• Chen TC, Castillo L, Korycka-Dahl M, DeLuca HF. Role of vitamin D metabolites in phosphate transport of rat intestine. J Nutr. 1974 Aug;104(8):1056-60. doi: 10.1093/jn/104.8.1056. No abstract available.

  PMID: 4854171 BACKGROUND

• Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special emphasis on dietary phosphorus intake. Semin Dial. 2007 Jul-Aug;20(4):295-301. doi: 10.1111/j.1525-139X.2007.00309.x.

  PMID: 17635818 BACKGROUND

• Borowitz SM, Ghishan FK. Phosphate transport in human jejunal brush-border membrane vesicles. Gastroenterology. 1989 Jan;96(1):4-10. doi: 10.1016/0016-5085(89)90757-9.

  PMID: 2909436 BACKGROUND

MeSH Terms

Conditions

Hypophosphatemia; Bone Diseases, Metabolic; Premature Birth

Interventions

Standard of Care; potassium phosphate; Solutions

Condition Hierarchy (Ancestors)

Phosphorus Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases; Musculoskeletal Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Pharmaceutical Preparations

Study Officials

• Alex Mullen

  University of Strathclyde

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helen Mactier, MB ChB

CONTACT

011441412115249; Helen.Mactier@ggc.scot.nhs.uk

Stewart I Watts, MPharm

CONTACT

011441415483577; stewart.watts@strath.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 23, 2012
• First Posted: August 31, 2012
• Study Start: February 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: August 31, 2012

Record last verified: 2012-08

Locations

GB (1)