Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
HPN-100 · 9 trials · 5 indications
Rate of adverse events during the Switch-Over portion of the Protocol
Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. Arm A day 14 and Arm B day 28 data were combined as a NaPBA treatment Arm. Arm B day 14 and Arm A day 28 data were combined as a HPN-100 treatment Arm.
To evaluate the safety and PK characteristics of HPN-100 compared with sodium phenylbutyrate (NaPBA) in pediatric patients with urea cycle disorders (UCDs)
Part A: The rate of AEs and tolerability of 6 mL and 9 mL doses of HPN-100 were considered the primary safety endpoints for Part A. Safety assessments included adverse events, laboratory tests (including ammonia, hematology, coagulation, liver function and serum chemistry parameters), vital signs, physical and neurological examinations, and electrocardiograms.
An HE event was defined as occurrences of either a West Haven (WH) Grade ≥2 or a WH Grade 1 and asterixis grade increase of 1 (if baseline WH = 0). The WH criteria are widely used for rating the severity of HE and are summarized below: Grade 1: trivial lack of awareness, euphoria or anxiety, shortened attention span, impaired performance of addition Grade 2: lethargy or apathy, minimal disorientation for time or place, subtle personality change, inappropriate behavior, impaired performance of subtraction Grade 3: somnolence to semi-stupor but responsive to verbal stimuli, confusion, gross disorientation Grade 4: coma (unresponsive to verbal or noxious stimuli) Asterixis was assessed after arm and forearm extension along with wrist dorsiflexion for 30 seconds and assigned a grade according to the following criteria: Grade 1: rare flaps Grade 2: occasional irregular flaps Grade 3: frequent flaps Grade 4: continuous flaps
Data were collected at pre-first dose and at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post first dose.
| Arm | Type | Description |
|---|---|---|
| HPN-100 | EXPERIMENTAL | Switch over from sodium phenylbutyrate to open label HPN-100 oral liquid over 10 days then open label, long term treatment for 12 months |
| Buphenyl (NaPBA) /HPN 100 Placebo | EXPERIMENTAL | Subjects in Arm A were randomly assigned to receive NaPBA + HPN 100 placebo for 2 weeks and then crossed over to receive HPN 100 + NaPBA Placebo for 2 weeks. |
| HPN-100/NaPBA Placebo | EXPERIMENTAL | Subjects in Arm B were randomly assigned to receive HPN-100 + NaPBA placebo for 2 weeks and then crossed over to receive NaPBA + HPN 100 placebo for 2 weeks. |
| HPN-100 and NaPBA | EXPERIMENTAL | 1 week of NaPBA treatment followed by 1 week of HPN-100 treatment. |
| Placebo | PLACEBO_COMPARATOR | - |
| BUPHENYL® to HPN-100 vs. HPN-100 | ACTIVE_COMPARATOR | Buphenyl treatment for one week was followed by dose escalation to HPN-100. Dose of Buphenyl was gradually decreased while HPN-100 dose was gradually increased until subject reached dosing of 100% HPN-100. HPN-100 at 100% of the dose was given for 1 week before subject was switched back to original Buphenyl treatment. |
| Arm 1 | PLACEBO_COMPARATOR | Cohort A: 9 mL HPN-100 or placebo Cohort B: 12 mL HPN-100 placebo |
| Arm 2 | PLACEBO_COMPARATOR | This study requires 4 periods. In each of the periods you will receive one of the dose groups listed below. At the completion of the study you will have participated in all 4 dose groups. The order in which you participate in each dose group will be randomly assigned. Dose Group A: 9 mL placebo via oral syringe 3 times daily for 3 days Dose Group B: single oral dose of 400 mg moxifloxacin on study Day 3 Dose Group C: 6 mL HPN-100 and 3 mL placebo via oral syringe 3 times daily for 3 days Dose Group D: 9 mL HPN-100 via oral syringe 3 times daily for 3 days |
| GT4P-F | EXPERIMENTAL | GT4P-F (80% GT4P) was supplied as an odorless, colorless, tasteless liquid oil in 125 ml bottles. This formulation was designed to be mixed in water and create a self-emulsifying suspension, thus administered in water for the trial. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-F was mixed in 50 ml of water, taken orally, and then the cup rinsed with 50 ml of water and taken orally. GT4P-F was stored at ambient temperature away from light. |
| GT4P-API | EXPERIMENTAL | GT4P-API was supplied as an odorless, colorless, tasteless oil in 125 ml bottles. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-API was taken orally and washed down with 100 ml of water. GT4P-API was stored at ambient temperature, away from light. |
| Ammonul | ACTIVE_COMPARATOR | Ammonul® was supplied as single-use glass vials of 10% sodium phenylacetate and 10% sodium benzoate for intravenous injection. Ammonul® was diluted before use with sterile dextrose injection 10% to a concentration of 9 mg/ml. Once diluted it was kept at room temperature and used within 24 hours. The dose was 2.75 g/m2 and was administered as an intravenous infusion over a 120-minute period. Ammonul® was stored at 25°C, within a range of 15-30°C. |
| Buphenyl | ACTIVE_COMPARATOR | Sodium phenylbutyrate or Buphenyl® was supplied as a white powder in 250 g bottles. The required amount of powder (equivalent to 3 g/m2 of PBA) was weighed out, mixed in 100 ml of water, and administered orally. Doses were calculated on a weight/volume basis and corrected for sodium content and purity. Buphenyl® was stored at ambient temperature. |
| Name | Type | Description |
|---|---|---|
| HPN-100 | DRUG | HPN-100 is a pro-drug of PAA that combines with glutamine to provide an alternative vehicle for waste nitrogen elimination. It is a liquid with minimal taste and odor. Approximately three teaspoons of HPN-100 (\~17.4 mL) delivers an equivalent amount as PBA that 40 tablets of NaPBA. |
| Buphenyl (NaPBA) | DRUG | Buphenyl (NaPBA) will be the comparator drug to HPN-100 in this study. |
| NaPBA | DRUG | NaPBA tablets for oral administration and NaPBA powder for oral, nasogastric, or gastrostomy tube administration contain the active ingredient sodium phenylbutyrate. NaPBA is a prodrug and is rapidly metabolized to PAA, the metabolically active compound that conjugates with glutamine via acetylation to form PAGN, which is excreted by the kidneys. |
| Placebo | DRUG | Part B: same as experimental arm |
| BUPHENYL® | DRUG | BUPHENYL® (sodium phenylbutyrate) tablets and powder have been approved for marketing in the United States since 1996 as an adjunctive therapy in the long-term management of patients with UCDs involving deficiencies of CPS, OTC, or ASS. |
| HPN-100 or Placebo | DRUG | single oral dose of 12 mL HPN-100 given via syringes 3 times daily for 3 days |
| Moxifloxacin | DRUG | single oral 400-mg dose on study Day 3 |
| Ammonul | DRUG | - |
| Buphenyl | DRUG | - |
Inclusion Criteria: * Male and female subjects 29 days to \< 6 years old. If the subject is born prematurely, calculation of the lower age limit begins at the corrected gestational age of 40 weeks. * Signed informed consent by the subject's legally acceptable representative * Suspected or confirmed...
HPN-100 is an investigational small molecule being studied for urea cycle disorders, cirrhosis, hepatic encephalopathy, and drug toxicity. It has been evaluated in clinical trials involving healthy volunteers and patients with these conditions. The drug is not approved and remains in clinical development.
HPN-100 is being developed by Amgen Inc., a biopharmaceutical company traded on NASDAQ under the ticker AMGN. Amgen is conducting clinical trials to evaluate the safety and efficacy of HPN-100 in various patient populations.
HPN-100 is in Phase 2 clinical development. It has completed Phase 1 and Phase 2 trials, with no active trials currently ongoing. The drug remains investigational and has not received FDA approval.
HPN-100 has been studied in several completed trials, including NCT00947544 in children with urea cycle disorders, NCT00977600 in healthy volunteers, NCT00986895 in subjects with hepatic impairment and cirrhosis, and NCT00999167 in subjects with cirrhosis and episodic hepatic encephalopathy.
Yes, HPN-100 is also known as glyceryl tri-(4-phenylbutyrate), abbreviated as GT4P. Clinical trials have used both names to refer to the same investigational drug, which is being studied for urea cycle disorders and related conditions.