NCT03121664

11 evidence topics · 7 sources

Objective

Trial objective: effect of itraconazole on PF-06649751 exposure

“The purpose of this study is to evaluate the impact of CYP3A4 inhibitor, itraconazole, on plasma concentration of PF-06649751 in healthy subjects” (opens the source at this quote in a new tab)

Location and study date

Summary: sponsor, site, and study dates

The registry record for NCT03121664 gives Pfizer as sponsor and B7601006 as the sponsor study number, with a single site, the Pfizer Clinical Research Unit in Brussels, Belgium. The actual study start date was 7 April 2017 and the actual study completion date was 14 September 2017, with 11 participants enrolled. No results have been posted to the registry.

Study design

Open-label, fixed-sequence design

“A Phase 1, Open-label, Fixed-sequence Study To Estimate The Effects Of Multiple-dose Administration Of Itraconazole On The Steady-state Pharmacokinetics Of Pf-06649751 In Healthy Adult Subjects” (opens the source at this quote in a new tab)

Eligibility criteria

Healthy adults

“Healthy female subjects of nonchildbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive.” (opens the source at this quote in a new tab)

Treatment

PF-06649751 titration and itraconazole coadministration

“PF-06649751 0.25 mg on Days 1,2,3 PF-06649751 0.5 mg on Days 4,5,6 PF-06649751 1 mg on Days 7 to Day 25 Itracoanzole 200 mg on Days 12 to Day 25” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using steady-state maximum concentration and area under the curve as the primary endpoint

Primary pharmacokinetic outcome measures

“PF-06649751 and PF-06752844 steady state Cmax” (opens the source at this quote in a new tab)
“PF-06649751 and PF-06752844 steady state AUC24” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Enrollment

Measure	Quoted record
Enrollment (actual)	“11”

Description of analysis sets

No evidence found.

Results

Participant disposition

No evidence found.

Baseline characteristics

No evidence found.

Efficacy results

Effect of strong CYP3A4 inhibition on tavapadon and metabolite exposure

“Tavapadon’s clearance is primarily via metabolism by cytochrome P450 (CYP450) 3A4 (CYP3A4). Coadministration with the potent CYP3A4 inhibitor itraconazole resulted in a 4- and 5-fold increase in peak and overall exposure, respectively; the major circulating hydroxylated metabolite exposure decreased by 36%.” (opens the source at this quote in a new tab)

Phase 1 pharmacokinetic summary across studies

“Following oral administration of tavapadon, PK was characterized by rapid absorption and average terminal elimination half-life of approximately 24 hours, supporting once-daily dosing. High-fat meals prior to dosing did not have clinically relevant impact on the rate or extent of absorption in healthy volunteers (a study in PD is ongoing).” (opens the source at this quote in a new tab)
“Due to low recovery of tavapadon in urine (<2%) and its extensive hepatic metabolism, planned studies will evaluate PK and safety in patients with severe renal impairment and patients with mild, moderate, or severe hepatic impairment.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

Not applicable.

Safety results

Safety across phase 1 studies

“Although nausea and vomiting are the most frequent adverse events, there were no notable abnormalities in laboratory or electrocardiogram parameters across early-phase studies. Tavapadon is generally safe and well tolerated in a titrated dose of up to 15 mg in PD.” (opens the source at this quote in a new tab)

Study limitations

Summary: limitations of the NCT03121664 evidence

The itraconazole result is available only as one sentence in a 2022 congress abstract that summarizes several phase 1 studies without naming them; no registry results, confidence intervals, or individual pharmacokinetic parameters have been published. The study enrolled 11 healthy adults aged 18 to 55 years and used a 1 mg PF-06649751 dose; the same abstract describes titrated doses of up to 15 mg in Parkinson's disease.