Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Keratosis, Actinic

Keratosis

Skin Diseases

Precancerous Conditions

Dermatologic Agents

All Drugs and Chemicals

Aminolevulinic Acid

Protoporphyrin IX

Photosensitizing Agents

Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid).

One single Photodynamic therapy (PDT).

Combination Product: Photodynamic therapy (PDT) using BF-RhodoLED® (ALA-PDT, Ameluz®-PDT).

BF-200 ALA and red light LED lamp

The aim of this study is to assess the pharmacokinetics (PK) of the parent drug 5-aminolevulinic acid (ALA) and its active metabolite protoporphyrin IX (PpIX) during photodynamic therapy with 3 tubes of BF-200 ALA 10% gel (Ameluz®) in combination with the BF-RhodoLED® lamp in the systemic circulation of diseased individuals presenting with actinic keratosis (AK) on the face/scalp or in the periphery (neck/trunk/extremities) along with subjects' safety/tolerability during and after treatment.

Study to Evaluate the Safety of BF-200 ALA (Ameluz®) for Photodynamic Therapy (PDT) in the Treatment of Expanded Fields of Actinic Keratosis (AK)

An Open-label Phase I Study to Evaluate the Pharmacokinetics of 5-aminolevulinic Acid and Protoporphyrin IX in Human Plasma Under Maximal Use Conditions After Topical Application of 3 Tubes of BF-200 ALA 10% Gel for Photodynamic Therapy (PDT) in Subjects Suffering From Actinic Keratosis

Blood samples for ALA analysis for each subject were collected, starting at Visit 1 and then 0.5h prior to BF-200 ALA application for up to 10h afterwards. The concentrations of ALA in plasma were measured by an analytical laboratory using validated, internally standardized liquid chromatography-tandem mass spectrometry methods.

Blood samples for PpIX analysis for each subject were collected, starting at Visit 1 and then 0.5h prior to BF-200 ALA application for up to 10h afterwards. The concentrations of PpIX in plasma were measured by an analytical laboratory using validated, internally standardized liquid chromatography-tandem mass spectrometry methods.

Parameter: AUC(0-t) (Area Under Curve); area under the baseline-adjusted plasma concentration-time curve from time zero to the last sampling time point at which the concentration was at or above lower limit of quantification; t(last) is defined as the last value \>0 after baseline adjustment.

Parameter: AUC(0-∞) (Area Under Curve); area under the baseline-adjusted plasma concentration-time data extrapolated to infinity

Parameter: %AUC(t-∞) (Area Under Curve); proportion of extrapolated part

Parameter: Cmax (Maximum Plasma Concentration); observed maximum baseline-adjusted plasma concentration

Parameter: λz (Elimination Rate Constant); λz denotes the terminal rate constant estimated by linear regression analysis from a range of concentrations in the terminal phase estimated for each treatment and subject by log-linear regression from the linear portion of the logarithmic transformed concentration-time plot. The algorithm will start with the last 3 points with quantifiable concentrations and increases the number of involved points by 1 until the time point after Cmax restricted on time points after removing of the BF-200 ALA gel (all PK samples after the gel is wiped off \[after 3h±10 min); λz was only determined in subjects in which the log-linear terminal phase could clearly be defined. Resulting unreliable parameters were flagged accordingly and not used in descriptive statistics. If any pharmacokinetic parameter should have been classified as unreliable, all calculations that use this parameter were considered missing.

Parameter: t1/2 (apparent terminal half-life); calculated by ln2/λz; t1/2 was only determined in subjects in which the log-linear terminal phase could clearly be defined. Resulting unreliable parameters were flagged accordingly and not used in descriptive statistics. If any pharmacokinetic parameter should have been classified as unreliable, all calculations that use this parameter were considered missing.

Frequency of treatment-emergent adverse events (TEAEs),including serious adverse events (SAEs).

Assessment of pain at the application site using an 11-point Numeric Rating Scale (NRS-11) ranging from 0 (no pain) to 10 (worst imaginable pain)

Application site reactions: discomfort (burning, pain, itching, stinging, warmth, others)

Application site reactions: skin reactions (erythema, edema, induration, vesicles, erosion, ulceration, scaling/flaking, scabbing/crusting, discharge/exudate, others); maximum severity of AE: mild, moderate, or severe

Biofrontera Bioscience GmbH

TEAEs (treatment emergent adverse events) are defined as all AEs or SAEs that occurred after lesion preparation at Visit 2, which was at maximum one hour before IMP application (i.e. AE onset date/time ≥ date/time of IMP application (Visit 2) - 1 h).

• Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid) • Each subject received three entire tubes of the IMP (2 g each, containing 156 mg ALA), resulting in a total dose of 468 mg ALA (free base) • The amount was sufficient to cover one treatment field (continuous field or discontinuous field with several patches), totaling approx. 60 cm² with BF-200 ALA gel at a thickness of approx. 1 mm • Treatment field(s) could be located on either the face/scalp or in the periphery (neck/trunk/extremities) excluding the genitalia (minimal distance of about 1 cm) • IMP dried for approx. 10 min • Subjects had to stay in a well-tempered environment during 3h incubation under light-blocking, occlusive dressing • Dressing was removed; remnant gel wiped off • Illumination with BF-RhodoLED® (10 min; 37 J/cm²) • In case of discontinuous treatment field(s), two BF-RhodoLED® lamps were used simultaneously • One single PDT was performed

Stratum: Face/Scalp

Stratum: Periphery

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Subjects' skin type was assessed at the screening visit using a six-level Fitzpatrick Skin Type Rating Scale, which ranges from very fair (skin type I) to very dark (skin type VI).

Fitzpatrick skin type

Clinical Trial Department

0.5h

1.5h

2.5h

3.5h

ALA Pharmacokinetic Set (PKS ALA): includes all subjects who had at least one evaluable pre-dose and post-dose pharmacokinetic sample (i.e., samples taken after the application of BF-200 ALA); a pre-dose/post-dose sample was regarded evaluable if the plasma concentration was at or above LLOQ.

Assessment of Baseline-adjusted Plasma Concentration-time Curves for ALA After a Single PDT Treatment Applying 3 Tubes of BF-200 ALA in Conjunction With the BF-RhodoLED® Under Maximal Use Conditions in Subjects With Mild to Severe Actinic Keratosis.

PpIX Pharmacokinetic Set (PKS PpIX): includes all subjects who had at least one evaluable pre-dose and post-dose pharmacokinetic sample (i.e., samples taken after the application of BF-200 ALA); a pre-dose/post-dose sample was regarded evaluable if the plasma concentration was at or above LLOQ.

Assessment of Baseline-adjusted Plasma Concentration-time Curves for PpIX After a Single PDT Treatment Applying 3 Tubes of BF-200 ALA in Conjunction With the BF-RhodoLED® Under Maximal Use Conditions in Subjects With Mild to Severe Actinic Keratosis.

Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.

Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.

Application site erythema

Application site exfoliation

Application site hyperaesthesia

Application site induration

Application site oedema

Application site pain

Application site paraesthesia

Application site pruritus

Application site scab

Application site vesicles

Application site warmth

Safety analysis set (SAF): includes all subjects who underwent at least one of the following treatment procedures: preparation of the treatment field(s), application of BF-200 ALA, or illumination. If the conduct of any treatment procedures was not certain, the subject was to be included in the SAF.

Assessment of the Frequency and Severity of All Treatment-emergent Adverse Events (TEAEs), Including Serious Adverse Events (SAEs) in Response to PDT With BF-200 ALA Under Maximal Use Conditions.

Assessment of Pain Intensity at the Application Site in Response to PDT With BF-200 ALA Under Maximal Use Conditions Using an 11-point Numeric Rating Scale (NRS-11), Where a Score of 0 Means "no Pain" and a Score of 10 Means "Worst Imaginable Pain".

Spots Global Cancer Trial Database for Study to Evaluate the Safety of BF-200 ALA (Ameluz®) for Photodynamic Therapy (PDT) in the Treatment of Expanded Fields of Actinic Keratosis (AK)

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