Scintigraphic evaluation of the performance of ALLN-346 Tablets

• Research type

  Research Study

• Full title

  A Phase 1, Single Centre, Two Part, Open Label, Crossover Study in Healthy Volunteers Using Scintigraphy to Characterise the In Vivo Performance of ALLN-346 Enteric Coated Tablets.

• IRAS ID

  302759

• Contact name

  Howard N.E. Stevens

• Contact email

  howard.stevens@bddpharma.com

• Sponsor organisation

  Allena Pharmaceuticals Inc

• Eudract number

  2021-003580-10

• Duration of Study in the UK

  1 years, 1 months, 28 days

• Research summary

  Research Summary

  This study seeks to investigate the gastrointestinal transit time and dissolution behaviours of ALLN-346 formulations and understand the impact of food effects. ALLN-346 is a non-absorbed urate degrading enzyme (urate oxidase) is currently in clinical development for the treatment of Hyperuricemia.

  It is usually available as enteric coated tablets contained within a capsule.
  
  The following treatments will be dosed as part of the study

  Treatment A: One ALLN-346 EC tablet (fast release), approximately 22.5 mg urate oxidase protein (Allena MAD formulation)
  Treatment B: One 90mg ALLN-346 HPMC capsule (containing four [fast release] ALLN-346 tablets, each approximately 22.5 mg urate oxidase protein)
  Treatment C: One ALLN-346 EC tablet (slow release), approximately 22.5 mg urate oxidase protein
  Treatment D: One ALLN-346 HPMC capsule (containing four [slow release] ALLN-346 tablets, each approximately 22.5 mg urate oxidase protein)

  This study consists of two parts (12 subjects in each part):

  Part One will evaluate two ALLN-346 formulations, a fast release and a slower sustained release. Subjects will receive a single tablet of each formulation and four tablets contained within a capsule.

  The primary purpose of this part of the study is to understand the gastrointestinal transit and disintegration behaviour of the formulations in vivo.

  Part Two will involve a second cohort of subjects and will comprise further scintigraphic studies on the formulation(s) from Part One in fasted and/or fed states. Subjects will attend a maximum of 4 assessment visits.
  
  In this study we will use scintigraphic imaging to visualise the gastric emptying of each treatment (when they leave the stomach) and confirm the site of release in the gastrointestinal tract. We will also use this technique to determine how quickly the treatment breaks up in the body. To look at these parameters we will add a small amount of radioactive material to the tablets.

  Summary of Results

  This was a phase 1, single centre, open label, crossover study in healthy volunteers using scintigraphy to characterize the in vivo performance of ALLN-346 enteric coated tablets.

  Twelve healthy male volunteers aged 18-65 years, inclusive, with a Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive, and free from any significant diseases including cardiac, renal and gastrointestinal disease were entered into the study. The first participant was enrolled on 15Dec2021 and the last participant completed on 23Feb2022. Of the twelve participant enrolled nine participants completed the study.

  The primary objective of this study was to assess survival of EC tablets in the stomach, and the site and time of onset of disintegration / release for the radiolabelled EC tablets in each ALLN-346 formulation in the fed state.

  Each participant who completed the study to received four treatments as follows (one at each assessment visit):
  Treatment A: One ALLN-346 EC tablet (fast release) with approximately 22.5 mg urate oxidase protein/tablet (Allena MAD formulation) Treatment B: One ALLN-346 HPMC capsule (containing four [fast release] ALLN-346 tablets, each approximately 22.5 mg urate oxidase protein, a total of approximately 90mg protein (Allena MAD formulation) Treatment C: One ALLN-346 EC tablet (slow release), approximately 22.5 mg urate oxidase protein/tablet

  The four treatments were tolerated well, and no serious AEs were reported in this study. Of the twelve participants treated, four participants (33%) experienced at least one AE. In total, seven adverse events were reported during the study that generally were mild including some nausea, vomiting, gastroesophageal reflux, dizziness. One participant reported an AE relating to COVID-19 which resolved prior to the first dosing. No AE resulted in discontinuation. No clinically significant changes in vital signs (blood pressure and heart rate), ECG or physical.

  Scintigraphic analysis of release and gastrointestinal behaviour of the formulation demonstrated that both formulations survived stomach pH conditions and emptied intact into the small intestine. Median tablet dispersion for both formulations was initiated around 55 min after gastric emptying and occurred in the ileum in the majority of cases. Median complete dispersion of SR tablets in-vivo was approximately 20 minutes slower than for the MAD formulation.

  The median transit time for dispersed ALLN-346 (4 tablets in the capsule) was >3 hours suggesting that most of the length of the small intestine is covered with ALLN-346 which is critical for the effective urate degradation that is secreted from circulation or formed along the length of the small intestine No intact tablets were identified in the colon from either formulation

• REC name

  London - London Bridge Research Ethics Committee

• REC reference

  21/LO/0538

• Date of REC Opinion

  4 Oct 2021

• REC opinion

  Further Information Favourable Opinion